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Mendeliome v1.4516 ANLN Zornitza Stark Publications for gene: ANLN were set to 24676636; 30002222; 34819827; 38322629; 37957688
Mendeliome v1.4515 ANLN Zornitza Stark edited their review of gene: ANLN: Added comment: PMID 41492027: two individuals from a single family with missense variant and FSGS phenotype. Insufficient segregation. Retain Amber rating as many of the previously reported variants have high pop frequencies.; Changed publications: 24676636, 30002222, 34819827, 38322629, 37957688, 41492027
Mendeliome v1.4515 AHR Zornitza Stark Publications for gene: AHR were set to 29726989; 31896775
Mendeliome v1.4514 AHR Zornitza Stark edited their review of gene: AHR: Added comment: PMID 38922562 reports third family with foveal hypoplasia, homozygous variant. Retain Amber rating.; Changed publications: 31009037, 33193710, 38922562
Mendeliome v1.4514 JKAMP Zornitza Stark Marked gene: JKAMP as ready
Mendeliome v1.4514 JKAMP Zornitza Stark Gene: jkamp has been classified as Green List (High Evidence).
Mendeliome v1.4514 Zornitza Stark Copied gene JKAMP from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.4514 JKAMP Zornitza Stark gene: JKAMP was added
gene: JKAMP was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: JKAMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JKAMP were set to 41643666
Phenotypes for gene: JKAMP were set to Neurodevelopmental disorder with seizures and impaired intellectual and language development, MIM# 621533
Mendeliome v1.4513 MDH1 Rylee Peters Publications for gene: MDH1 were set to 31538237
Mendeliome v1.4512 MDH1 Rylee Peters reviewed gene: MDH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 40959467, 31538237; Phenotypes: Developmental and epileptic encephalopathy 88, MIM#618959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4512 LMNB1 upstream region Sarah Milton Region: LMNB1 upstream region was added
Region: LMNB1 upstream region was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: LMNB1 upstream region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: LMNB1 upstream region were set to PMID: 30842973; 30697589; 25701871
Phenotypes for Region: LMNB1 upstream region were set to Adult-onset autosomal dominant demyelinating leukodystrophy, MONDO:0008215
Review for Region: LMNB1 upstream region was set to GREEN
Added comment: LMNB1 encodes an intermediate filament proteins which play a role in forming the nuclear lamina lining the inner nuclear membrane. Overexpression of LMNB1 via gene duplication has been well established to cause adult-onset autosomal dominant demyelinating leukodystrophy, MONDO:0008215.

PMID: 30842973; 30697589; 25701871 report deletional forms of the phenotype. With an approx 167kb minimal critical region upstream of LMNB1 that has been associated with adult-onset autosomal dominant demyelinating leukodystrophy in 5 families with over 35 individuals affected.

The deletion is upstream of the promoter of LMNB1 and involves other protein coding genes (ALDH7A1/PHAX) that are thought to be bystanders. The proposed molecular mechanism of disease for these deletions is disruption of a topologically associated domain boundary resulting in overexpression of LMNB1. This occurs by placing the promoter in closer proximity to an upstream enhancer element.

Extensive functional studies support this hypothesis and affected individuals have been shown to have upregulated LMNB1 protein on Western blot.

Note the coordinates differ between families with much larger deletions reported in many affected individuals.
Sources: Literature
Mendeliome v1.4511 FRMD4A Sangavi Sivagnanasundram reviewed gene: FRMD4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34869127; Phenotypes: severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, MONDO:0014787; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4511 FAM92A Sangavi Sivagnanasundram reviewed gene: FAM92A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38853702; Phenotypes: Polydactyly, postaxial, type A9, MONDO:0032603; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4511 TNNI1 Sarah Milton reviewed gene: TNNI1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30886088; Phenotypes: Sudden unexpected infant death, MONDO:1010116, TNNI1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4511 ADIPOR1 Zornitza Stark Phenotypes for gene: ADIPOR1 were changed from Retinitis pigmentosa to Retinitis pigmentosa, MONDO:0019200, ADIPOR1-related; Hypertrophic cardiomyopathy, MONDO:0005045, ADIPOR1-related
Mendeliome v1.4510 ADIPOR1 Zornitza Stark Publications for gene: ADIPOR1 were set to 27655171; 26662040
Mendeliome v1.4509 ADIPOR1 Zornitza Stark edited their review of gene: ADIPOR1: Added comment: PMID 33523960 reports five individuals from four unrelated South‑Asian families carrying heterozygous missense variants (c.470T>A p.L157H, c.436G>A p.V146M, c.433T>A p.F145I) who present with HCM; three of the five also have diabetes mellitus. All variants are absent or ultra‑rare in public databases, three are de novo events, and functional assays in rat cardiomyocytes and a Cre‑V146M transgenic mouse model show hyperactivation of p38/mTOR and/or ERK pathways, cardiomyocyte hypertrophy, metabolic dysregulation and rescue by rapamycin.; Changed publications: 27655171, 26662040, 33523960; Changed phenotypes: Retinitis pigmentosa, MONDO:0019200, ADIPOR1-related, Hypertrophic cardiomyopathy, MONDO:0005045, ADIPOR1-related
Mendeliome v1.4509 CYS1 Lucy Spencer Classified gene: CYS1 as Green List (high evidence)
Mendeliome v1.4509 CYS1 Lucy Spencer Gene: cys1 has been classified as Green List (High Evidence).
Mendeliome v1.4508 CYS1 Lucy Spencer Phenotypes for gene: CYS1 were changed from Polycystic kidney disease, MONDO:0020642 to Polycystic kidney disease MONDO:0020642, CYS1-related
Mendeliome v1.4507 CYS1 Lucy Spencer Publications for gene: CYS1 were set to 34521872
Mendeliome v1.4506 CYS1 Lucy Spencer reviewed gene: CYS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41720266, 34521872; Phenotypes: Polycystic kidney disease MONDO:0020642, CYS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4506 FAM20B Sangavi Sivagnanasundram changed review comment from: 5 affected individuals from 2 unrelated families with autosomal recessive biallelic loss‑of‑function FAM20B variants presenting with lethal Desbuquois‑like skeletal dysplasia (short limbs, joint dislocations, craniofacial anomalies, intra‑uterine or neonatal death).

Gene upgraded to green in combination with previous reports of affected individuals and functional reports.; to: 5 affected individuals from 2 unrelated families with autosomal recessive biallelic loss‑of‑function FAM20B variants presenting with lethal Desbuquois‑like skeletal dysplasia (short limbs, joint dislocations, craniofacial anomalies, intra‑uterine or neonatal death).

Gene to remain as AMBER due to the potential overlap in families between the publications.
Mendeliome v1.4506 RCAN1 Lucy Spencer Phenotypes for gene: RCAN1 were changed from FSGS; proteinuria to Focal segmental glomerulosclerosis MONDO:0100313, RCAN1-related
Mendeliome v1.4505 RCAN1 Lucy Spencer edited their review of gene: RCAN1: Added comment: PMID: 33863784 both missense reported in this paper are present in gnomad, 1 with over 100 hets the other with over 1000. this gene is borderline red; Changed rating: AMBER; Changed publications: 33863784; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4505 DISC1 Zornitza Stark Phenotypes for gene: DISC1 were changed from {Schizophrenia 9, susceptibility to} MIM#604906 to {Schizophrenia 9, susceptibility to} MIM#604906; Corpus callosum agenesis, MONDO:0009022, DISC1-related
Mendeliome v1.4504 DISC1 Zornitza Stark Publications for gene: DISC1 were set to 18945897
Mendeliome v1.4503 DISC1 Zornitza Stark Mode of inheritance for gene: DISC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4502 DISC1 Zornitza Stark reviewed gene: DISC1: Rating: RED; Mode of pathogenicity: None; Publications: 21739582; Phenotypes: Corpus callosum agenesis, MONDO:0009022, DISC1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4502 DST Zornitza Stark Phenotypes for gene: DST were changed from Neuropathy, hereditary sensory and autonomic, type VI, MIM#614653; Epidermolysis bullosa simplex, autosomal recessive 2, MIM#615425; congenital myopathy MONDO:0019952, DST-related to Neuropathy, hereditary sensory and autonomic, type VI, MIM#614653; Epidermolysis bullosa simplex, autosomal recessive 2, MIM#615425; Congenital myopathy 29 with contractures, MIM# 621510; Lethal congenital contracture syndrome 12, MIM# 621511
Mendeliome v1.4501 DST Zornitza Stark edited their review of gene: DST: Added comment: The milder disorder is caused by variants that disrupt the DST-b isoform, while variants that affect both the DST-b and neuronal DST-a isoforms cause lethal congenital contracture syndrome.; Changed phenotypes: Neuropathy, hereditary sensory and autonomic, type VI, MIM#614653, Epidermolysis bullosa simplex, autosomal recessive 2, MIM#615425, Congenital myopathy 29 with contractures, MIM# 621510, Lethal congenital contracture syndrome 12, MIM# 621511
Mendeliome v1.4501 TUFT1 Krithika Murali Publications for gene: TUFT1 were set to 36689522
Mendeliome v1.4500 TUFT1 Krithika Murali Classified gene: TUFT1 as Green List (high evidence)
Mendeliome v1.4500 TUFT1 Krithika Murali Gene: tuft1 has been classified as Green List (High Evidence).
Mendeliome v1.4499 TUFT1 Krithika Murali reviewed gene: TUFT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37716648, 36689526, 36689522; Phenotypes: Woolly hair-skin fragility syndrome - MIM#620415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4499 RBFOX3 Lucy Spencer Publications for gene: RBFOX3 were set to 35951651; 36117209; 24039908
Mendeliome v1.4498 RBFOX3 Lucy Spencer reviewed gene: RBFOX3: Rating: AMBER; Mode of pathogenicity: None; Publications: 40011789, 36117209; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4498 PRPH Lucy Spencer Publications for gene: PRPH were set to 20363051; 15322088; 15446584
Mendeliome v1.4497 PRPH Lucy Spencer Phenotypes for gene: PRPH were changed from {Amyotrophic lateral sclerosis, susceptibility to}, 105400 to {Amyotrophic lateral sclerosis, susceptibility to} MIM#105400; Hereditary motor and sensory neuropathy MONDO:0015358, PRPH-related
Mendeliome v1.4496 PRPH Lucy Spencer reviewed gene: PRPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 30992453, 32638105; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to} MIM#105400, Hereditary motor and sensory neuropathy MONDO:0015358, PRPH-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4496 TDP1 Zornitza Stark Publications for gene: TDP1 were set to 31182267; 12244316
Mendeliome v1.4495 PRPF6 Lucy Spencer Publications for gene: PRPF6 were set to 21549338; 32335390
Mendeliome v1.4494 PRPF6 Lucy Spencer Classified gene: PRPF6 as Green List (high evidence)
Mendeliome v1.4494 PRPF6 Lucy Spencer Gene: prpf6 has been classified as Green List (High Evidence).
Mendeliome v1.4493 PRPF6 Lucy Spencer reviewed gene: PRPF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21549338, 32335390, 36012314, 41584402; Phenotypes: Retinitis pigmentosa 60 MIM#613983; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4493 TDP1 Zornitza Stark changed review comment from: Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) is an autosomal recessive neurologic disorder characterized by onset of gait disturbances in the first or second decades of life. Affected individuals have cerebellar ataxia associated with cerebellar atrophy on brain imaging, as well as an axonal sensorimotor neuropathy with distal sensory impairment, hypo- or areflexia, pes cavus, and steppage gait.

Three families reported, however all from Middle East and had same homozygous missense variant.; to: Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) is an autosomal recessive neurologic disorder characterized by onset of gait disturbances in the first or second decades of life. Affected individuals have cerebellar ataxia associated with cerebellar atrophy on brain imaging, as well as an axonal sensorimotor neuropathy with distal sensory impairment, hypo- or areflexia, pes cavus, and steppage gait.

Three families reported, however all from Middle East and had same homozygous missense variant p.H493R.
Mendeliome v1.4493 TDP1 Zornitza Stark edited their review of gene: TDP1: Added comment: Additional family reported in PMID 39576382 with different homozygous missense, c.1432C>T (p.His478Tyr). The affected individual had severe hypotonia, ataxia, distal axonal neuropathy, seizures at 9‑10 months, kyphoscoliosis, hearing/vision loss and moderate cognitive impairment. No other supportive data.; Changed publications: 31182267, 12244316, 39576382
Mendeliome v1.4493 STX4 Zornitza Stark Publications for gene: STX4 were set to 36355422
Mendeliome v1.4492 STX4 Zornitza Stark edited their review of gene: STX4: Added comment: PMID 35599850: two unrelated families were identified with biallelic STX4 variants: Family 1 with a homozygous missense c.718C>T (p.Arg240Trp) and Family 2 compound heterozygous c.89_90delGC (p.Gly30Aspfs*28) and c.232+4A>C (splice‑site). Affected individuals present with early‑onset dilated cardiomyopathy, ventricular arrhythmia, sensorineural hearing loss, global developmental delay, hypotonia and multiple congenital anomalies; the second individual died perinatally. CRISPR‑generated stx4‑null zebrafish recapitulate cardiac dysfunction, bradycardia, reduced vesicle docking and altered Ca²⁺ handling. Transgenic rescue with wild‑type stx4 restores phenotype, whereas the R241W (human R240W) allele is hypomorphic and only partially rescues, supporting a loss‑of‑function mechanism. Pharmacologic L‑type Ca²⁺ channel modulation ameliorated bradycardia, further underscoring functional loss of STX4.

Unclear if this is a separate disease association or whether it will be part of a spectrum with the previous isolated deafness reports.; Changed rating: AMBER; Changed publications: 36355422, 35599850; Changed phenotypes: Deafness, autosomal recessive 123, MIM# 620745; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4492 SFTPA1 Lucy Spencer reviewed gene: SFTPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31601679; Phenotypes: Interstitial lung disease 1 MIM#619611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4492 TDRD6 Sarah Milton reviewed gene: TDRD6: Rating: GREEN; Mode of pathogenicity: None; Publications: 39764564, 39331689, 38341271; Phenotypes: Infertility disorder, MONDO:0005047, TDRD6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4492 TDRD12 Sarah Milton reviewed gene: TDRD12: Rating: GREEN; Mode of pathogenicity: None; Publications: 40750267, 39122675; Phenotypes: Spermatogenic failure, MONDO:0004983, TDRD12-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4492 SREBF2 Zornitza Stark Phenotypes for gene: SREBF2 were changed from Neurocutaneous syndrome, MONDO:0042983, SREBF2-related to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related; Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related
Mendeliome v1.4491 SREBF2 Zornitza Stark Publications for gene: SREBF2 were set to 38847193
Mendeliome v1.4490 SREBF2 Zornitza Stark Mode of inheritance for gene: SREBF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4489 SREBF2 Zornitza Stark edited their review of gene: SREBF2: Added comment: PMID 39814172: reports three homozygous missense variants (p.L604W, p.T984A, p.S517F) in three unrelated families (two consanguineous families). Detailed clinical descriptions are provided for two families: Family 1 (two affected siblings, onset 39 y and 25 y, progressive spastic gait, pyramidal signs, no cognitive or peripheral neuropathy) and Family 2 (single female, onset 24 y, spastic gait, internal foot deformity, normal cognition). All carriers are asymptomatic. Functional assays in patient‑derived fibroblasts show increased mature SREBP2, cholesterol accumulation, and autophagosome/lysosome enlargement. Overexpression of the nuclear SREBP2 in Drosophila recapitulates locomotor deficits. The authors conclude that biallelic SREBF2 missense variants cause an autosomal recessive hereditary spastic paraplegia through gain‑of‑function overactivation of SREBP2.; Changed publications: 38847193, 39814172; Changed phenotypes: Neurocutaneous syndrome, MONDO:0042983, SREBF2-related, Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4489 SEC23A Zornitza Stark Publications for gene: SEC23A were set to 16980979; 21039434; 16980978; 27148587
Mendeliome v1.4488 SEC23A Zornitza Stark Mode of inheritance for gene: SEC23A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4487 SEC23A Zornitza Stark edited their review of gene: SEC23A: Changed rating: AMBER
Mendeliome v1.4487 SEC23A Zornitza Stark changed review comment from: Four families (two AR, two de novo AD) with consistent craniofacial, skeletal and ophthalmologic features. Functional data from zebrafish knock‑down.; to: Four families (two AR, two AD) with consistent craniofacial, skeletal and ophthalmologic features. Functional data from zebrafish knock‑down.
Mendeliome v1.4487 SEC23A Zornitza Stark reviewed gene: SEC23A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38275611, 37828500, 34580982; Phenotypes: Craniolenticulosutural dysplasia, MIM# 607812; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4487 REC8 Zornitza Stark Classified gene: REC8 as Amber List (moderate evidence)
Mendeliome v1.4487 REC8 Zornitza Stark Gene: rec8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4486 TUB Krithika Murali Publications for gene: TUB were set to 24375934; 28852204
Mendeliome v1.4485 TUB Krithika Murali Phenotypes for gene: TUB were changed from Retinal dystrophy and obesity, MIM# 616188 to inherited retinal dystrophy - MONDO:0019118, TUB-related
Mendeliome v1.4484 TUB Krithika Murali Classified gene: TUB as Green List (high evidence)
Mendeliome v1.4484 TUB Krithika Murali Gene: tub has been classified as Green List (High Evidence).
Mendeliome v1.4483 TUB Krithika Murali changed review comment from: Additional unrelated individuals identified

PMID: 36650547 Xu et al 2023 report a homozygous variant (NM_003320.4, c.1379A>G, p.Asn460Ser) in an individual of Chinese ancestry with retinitis pigmentosa. No obesity

PMID: 36498982 Ziccardi et al 2022 report a homozygous splice variant in a 35 yo M of European descent with retinal dystrophy and elevated BMI.; to: Additional unrelated individuals identified

PMID: 36650547 Xu et al 2023 report a homozygous variant (NM_003320.4, c.1379A>G, p.Asn460Ser) in an individual of Chinese ancestry with retinitis pigmentosa. No obesity

PMID: 36498982 Ziccardi et al 2022 report a homozygous splice variant in a 35 yo M of European descent with retinal dystrophy and elevated BMI.
Mendeliome v1.4483 TUB Krithika Murali reviewed gene: TUB: Rating: GREEN; Mode of pathogenicity: None; Publications: 36498982, 32956375; Phenotypes: Retinal dystrophy and obesity - MIM#616188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4483 SVIL Sarah Milton reviewed gene: SVIL: Rating: AMBER; Mode of pathogenicity: None; Publications: 39554508, 36778260, 32779703; Phenotypes: Hypertrophic cardiomyopathy MONDO:0005045, myofibrillar myopathy 10, MONDO:0033620; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4483 ITPR3 Lucy Spencer reviewed gene: ITPR3: Rating: RED; Mode of pathogenicity: None; Publications: 36302985; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4483 OXGR1 Rylee Peters reviewed gene: OXGR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36571463; Phenotypes: Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis, MIM# 620374; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4483 TRAPPC2L Krithika Murali Phenotypes for gene: TRAPPC2L were changed from Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331 to Neurodevelopmental disorder - MONDO:0700092, TRAPPC2L-related
Mendeliome v1.4482 TRAPPC2L Krithika Murali Publications for gene: TRAPPC2L were set to 30120216; 32843486
Mendeliome v1.4481 TRAPPC2L Krithika Murali Classified gene: TRAPPC2L as Green List (high evidence)
Mendeliome v1.4481 TRAPPC2L Krithika Murali Gene: trappc2l has been classified as Green List (High Evidence).
Mendeliome v1.4480 TRAPPC2L Krithika Murali reviewed gene: TRAPPC2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 36849228, 32843486, 30120216; Phenotypes: Neurodevelopmental disorder - MONDO:0700092, TRAPPC2L-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4480 REC8 Zornitza Stark changed review comment from: PMID 35172124 reports homozygous frameshift deletion presenting with non‑obstructive azoospermia and meiotic arrest in a single affected individual. Further individual in PMID 31479588, but with homozygous missense.; to: PMID 35172124 reports homozygous frameshift deletion presenting with non‑obstructive azoospermia and meiotic arrest in a single affected individual. Further individual in PMID 31479588, but with het missense with relatively high pop frequency, discounted.
Mendeliome v1.4480 REC8 Zornitza Stark edited their review of gene: REC8: Changed rating: AMBER
Mendeliome v1.4480 REC8 Zornitza Stark Phenotypes for gene: REC8 were changed from Primary ovarian insufficiency to Infertility disorder, MONDO:0005047, REC8-related
Mendeliome v1.4479 REC8 Zornitza Stark Publications for gene: REC8 were set to 34794894; 15515002; 34707299
Mendeliome v1.4478 REC8 Zornitza Stark Classified gene: REC8 as Green List (high evidence)
Mendeliome v1.4478 REC8 Zornitza Stark Gene: rec8 has been classified as Green List (High Evidence).
Mendeliome v1.4477 REC8 Zornitza Stark reviewed gene: REC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35172124, 31479588; Phenotypes: Infertility disorder, MONDO:0005047, REC8-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4477 FOXF1 upstream regulatory region Sarah Milton Variant type for FOXF1 upstream regulatory region was changed from small to cnv_loss.
Mendeliome v1.4476 FOXF1 upstream regulatory region Sarah Milton Region: FOXF1 upstream regulatory region was added
Region: FOXF1 upstream regulatory region was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: FOXF1 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: FOXF1 upstream regulatory region were set to PMID: 27822317, 27071622, 23034409, 24842713
Phenotypes for Region: FOXF1 upstream regulatory region were set to Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380
Review for Region: FOXF1 upstream regulatory region was set to GREEN
Added comment: FOXF1 is a transcription factor involved in maintaining endothelial barrier through activation of S1P/S1PR1 signalling for integrity of adherens junctions.

An approximately 60kb enhancer 270kb upstream of the FOXF1 gene has been identified with copy number changes in this region seen in over 10 affected individuals with biopsy confirmed alveolar capillary dysplasia with misalignment of pulmonary veins.
Interestingly a large number of the deletions identified were de novo on the maternal allele.

Deletion size ranged between 104kb to 2625kb, coordinates from this entry are from a minimal overlapping region.

The enhancer region has binding motifs for a number of transcription factors, as well as this there is a non coding RNA (LINC01081) within the region that is thought to play a role with regulation of FOXF1 transcription. Supportive functional studies with RNAi-mediated knock-down of LINC01081 in normal fetal lung fibroblasts showed that this lncRNA positively regulates FOXF1 transcript level.
Sources: Literature
Mendeliome v1.4475 SLC13A1 Lucy Spencer Publications for gene: SLC13A1 were set to 36175384
Mendeliome v1.4474 RHOXF1 Lucy Spencer reviewed gene: RHOXF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28171600; Phenotypes: Spermatogenic failure, MONDO:0004983, RHOXF1-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.4474 PRDM15 Lucy Spencer Phenotypes for gene: PRDM15 were changed from Steroid-resistant nephrotic syndrome MONDO:0044765, PRDM15-related; Galloway-Mowat syndrome MONDO:0009627, PRDM15-related to Galloway-Mowat syndrome MONDO:0009627, PRDM15-related
Mendeliome v1.4473 PRDM15 Lucy Spencer reviewed gene: PRDM15: Rating: GREEN; Mode of pathogenicity: None; Publications: 31950080, 33593823; Phenotypes: Galloway-Mowat syndrome MONDO:0009627, PRDM15-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4473 PRDM15 Lucy Spencer Deleted their review
Mendeliome v1.4473 PRDM15 Lucy Spencer changed review comment from: PMID: 33593823- Reports the same families as PMID:31950080. 4 families homozygous for C844Y who had syndromic SRNS which this paper described as Galloway-Mowat syndrome, and another 2 homozygous for M154K or E190K who had isolated SRNS. Paper suggests the more severe phenotype associated with C844Y is because it affects a Cys residue in a zinc finger domain and was shown to destabilize the protein while also interfering with transcriptional activity while the other 2 missense in the SET domain decrease protein stability but do not affect transcriptional activity. In knock-out cell lines pronephric development was disrupted and could be rescued by WT but not by any of the 3 patient missense variants.

Borderline amber/green; to: PMID: 33593823- Reports the same families as PMID:31950080. 4 families homozygous for C844Y who had syndromic SRNS which this paper described as Galloway-Mowat syndrome, and another 2 homozygous for M154K or E190K who had isolated SRNS. Paper suggests the more severe phenotype associated with C844Y is because it affects a Cys residue in a zinc finger domain and was shown to destabilize the protein while also interfering with transcriptional activity while the other 2 missense in the SET domain decrease protein stability but do not affect transcriptional activity. In knock-out cell lines pronephric development was disrupted and could be rescued by WT but not by any of the 3 patient missense variants.

Borderline amber/green, likely 1 spectrum of disease
Mendeliome v1.4473 PRDM15 Lucy Spencer Phenotypes for gene: PRDM15 were changed from Multiple congenital anomalies MONDO:0019042, PRDM15-related to Steroid-resistant nephrotic syndrome MONDO:0044765, PRDM15-related; Galloway-Mowat syndrome MONDO:0009627, PRDM15-related
Mendeliome v1.4472 PRDM15 Lucy Spencer Classified gene: PRDM15 as Green List (high evidence)
Mendeliome v1.4472 PRDM15 Lucy Spencer Gene: prdm15 has been classified as Green List (High Evidence).
Mendeliome v1.4471 PRDM15 Lucy Spencer reviewed gene: PRDM15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33593823, 31950080; Phenotypes: Steroid-resistant nephrotic syndrome MONDO:0044765, PRDM15-related, Galloway-Mowat syndrome MONDO:0009627, PRDM15-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4471 PPP1R15B Lucy Spencer Publications for gene: PPP1R15B were set to 26159176; 26307080; 27640355
Mendeliome v1.4470 PPP1R15B Lucy Spencer Classified gene: PPP1R15B as Green List (high evidence)
Mendeliome v1.4470 PPP1R15B Lucy Spencer Gene: ppp1r15b has been classified as Green List (High Evidence).
Mendeliome v1.4469 PPP1R15B Lucy Spencer reviewed gene: PPP1R15B: Rating: GREEN; Mode of pathogenicity: None; Publications: 38159565, 26159176, 26307080, 27640355, 40568171; Phenotypes: Microcephaly, short stature, and impaired glucose metabolism 2, MIM#616817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4469 TRAF3IP2 Krithika Murali Publications for gene: TRAF3IP2 were set to 24120361; 31292894; 20660351
Mendeliome v1.4468 TRAF3IP2 Krithika Murali Classified gene: TRAF3IP2 as Green List (high evidence)
Mendeliome v1.4468 TRAF3IP2 Krithika Murali Gene: traf3ip2 has been classified as Green List (High Evidence).
Mendeliome v1.4467 TRAF3IP2 Krithika Murali reviewed gene: TRAF3IP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34289170, 33825088, 33359359, 32350852, 31292894, 30237576, 28640246; Phenotypes: candidiasis, familial, 8, MONDO:0014230, ?Candidiasis, familial, 8 - MIM#615527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4467 TRAC Krithika Murali Phenotypes for gene: TRAC were changed from Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387 to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387; TCR-alpha-beta-positive T-cell deficiency, MONDO:0014160
Mendeliome v1.4466 TRAC Krithika Murali Publications for gene: TRAC were set to 21206088
Mendeliome v1.4465 TRAC Krithika Murali Classified gene: TRAC as Green List (high evidence)
Mendeliome v1.4465 TRAC Krithika Murali Gene: trac has been classified as Green List (High Evidence).
Mendeliome v1.4464 TRAC Krithika Murali reviewed gene: TRAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41103553, 33909184; Phenotypes: TCR-alpha-beta-positive T-cell deficiency, MONDO:0014160, Immunodeficiency 7, TCR-alpha/beta deficient 615387; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4464 TPCN2 Krithika Murali Phenotypes for gene: TPCN2 were changed from [Skin/hair/eye pigmentation 10, blond/brown hair] MIM#612267 to albinism, TPCN2-related - MONDO:0043209
Mendeliome v1.4463 TPCN2 Krithika Murali reviewed gene: TPCN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 39809949, 36641477; Phenotypes: albinism, MONDO:0043209; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4463 EXOSC10 Sangavi Sivagnanasundram reviewed gene: EXOSC10: Rating: AMBER; Mode of pathogenicity: None; Publications: 41609100; Phenotypes: premature ovarian insufficiency MONDO:0019852; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4463 ERBB4 Sangavi Sivagnanasundram reviewed gene: ERBB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 38291418, 36123965, 35873773, 33414559, 32638105, 31432357, 29483666; Phenotypes: amyotrophic lateral sclerosis type 19, MONDO:0014223, Hirschsprung disease MONDO:0018309, idiopathic hypogonadotropic hypogonadism MONDO:0018555; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4463 DMRT2 Zornitza Stark Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230,DMRT2-related to Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523
Mendeliome v1.4462 DMRT2 Zornitza Stark edited their review of gene: DMRT2: Changed rating: GREEN
Mendeliome v1.4462 DMRT2 Zornitza Stark reviewed gene: DMRT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4462 ATP2B3 Bryony Thompson changed review comment from: PMIDs 25953895, 27653636, 28807751, 36207321 and 37821930 report 11 patients from 8 unrelated families with hemizygous ATP2B3 missense variants causing early‑onset cerebellar ataxia, hypotonia, developmental delay and sometimes seizures or dystonia. 2 of the patients had alternate diagnoses in PMM2 & LAMA1. Functional studies (HeLa Ca2+ assays, yeast complementation, homology modelling) demonstrate loss‑of‑function or altered pump activity. Single reports also link ATP2B3 to autism (PMID 28720891) and fetal akinesia (PMID 31680123).; to: PMIDs 25953895, 27653636, 28807751, 36207321 and 37821930 report 11 patients from 8 unrelated families with hemizygous ATP2B3 missense variants causing early‑onset cerebellar ataxia, hypotonia, developmental delay and sometimes seizures or dystonia. 2 of the patients had alternate diagnoses in PMM2 & LAMA1. Functional studies (HeLa Ca2+ assays, yeast complementation, homology modelling) demonstrate loss‑of‑function or altered pump activity. Single reports also link ATP2B3 to autism (PMID 28720891) and fetal akinesia (PMID 31680123).
Mendeliome v1.4462 ATP2B3 Bryony Thompson Deleted their comment
Mendeliome v1.4462 ATP2B3 Bryony Thompson Classified gene: ATP2B3 as Green List (high evidence)
Mendeliome v1.4462 ATP2B3 Bryony Thompson Gene: atp2b3 has been classified as Green List (High Evidence).
Mendeliome v1.4461 ATP2B3 Bryony Thompson Publications for gene: ATP2B3 were set to 22912398; 27653636; 27632770
Mendeliome v1.4460 ATP2B3 Bryony Thompson edited their review of gene: ATP2B3: Added comment: PMIDs 25953895, 27653636, 28807751, 36207321 and 37821930 report 11 patients from 8 unrelated families with hemizygous ATP2B3 missense variants causing early‑onset cerebellar ataxia, hypotonia, developmental delay and sometimes seizures or dystonia. 2 of the patients had alternate diagnoses in PMM2 & LAMA1. Functional studies (HeLa Ca2+ assays, yeast complementation, homology modelling) demonstrate loss‑of‑function or altered pump activity. Single reports also link ATP2B3 to autism (PMID 28720891) and fetal akinesia (PMID 31680123).; Changed rating: GREEN; Changed publications: 37821930, 36207321, 31680123, 28807751, 28720891, 27653636, 25953895; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, Syndromic disease, MONDO:0002254, X-linked progressive cerebellar ataxia, MONDO:0010547; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.4460 ARPC3 Bryony Thompson Publications for gene: ARPC3 were set to 36928819; 26166300
Mendeliome v1.4459 AQP1 Bryony Thompson Classified gene: AQP1 as Green List (high evidence)
Mendeliome v1.4459 AQP1 Bryony Thompson Gene: aqp1 has been classified as Green List (High Evidence).
Mendeliome v1.4458 AQP1 Bryony Thompson reviewed gene: AQP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40229839, 37007933, 35811711, 35627312, 35346192, 29650961; Phenotypes: pulmonary arterial hypertension, MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4458 EXOC8 Zornitza Stark Marked gene: EXOC8 as ready
Mendeliome v1.4458 EXOC8 Zornitza Stark Gene: exoc8 has been classified as Green List (High Evidence).
Mendeliome v1.4458 CASP10 Zornitza Stark Classified gene: CASP10 as Amber List (moderate evidence)
Mendeliome v1.4458 CASP10 Zornitza Stark Gene: casp10 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4457 GRK2 Zornitza Stark Publications for gene: GRK2 were set to 33200460
Mendeliome v1.4456 GRK2 Zornitza Stark Classified gene: GRK2 as Green List (high evidence)
Mendeliome v1.4456 GRK2 Zornitza Stark Gene: grk2 has been classified as Green List (High Evidence).
Mendeliome v1.4455 GRK2 Teresa Zhao changed review comment from: PMID 38647386 (2024): a novel homozygous p.(Arg474Ter) reported in an individual with Jeune ATD. Both parents are healthy carriers. Additional features include Morgagni hernia and an organoaxial-type rotation anomaly of the stomach and mid-gut malrotation. Same patient has been reported again in PMID: 38585547.; to: PMID 38647386 (2024): a novel homozygous p.(Arg474Ter) reported in an individual with Jeune ATD. Both parents are healthy carriers. Additional features include Morgagni hernia and an organoaxial-type rotation anomaly of the stomach and mid-gut malrotation. Same patient has been reported again in PMID: 38585547.
Mendeliome v1.4455 PPP1R12A Zornitza Stark Phenotypes for gene: PPP1R12A were changed from Intellectual disability; holoprosencephaly; disorder of sex development to Genitourinary and/or/brain malformation syndrome MIM#618820
Mendeliome v1.4454 MCAT Rylee Peters reviewed gene: MCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 36881526, 33918393, 31915829; Phenotypes: Optic atrophy 15, MIM# 620583, Mitochondrial disease (MONDO:0044970), MCAT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4454 GRK2 Teresa Zhao reviewed gene: GRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38647386; Phenotypes: Jeune asphyxiating thoracic dystrophy (ATD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4454 CASP10 Chern Lim reviewed gene: CASP10: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune lymphoproliferative syndrome, type II, MIM#603909; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.4454 PMP22 Zornitza Stark Publications for gene: PMP22 were set to 32356557
Mendeliome v1.4453 PMP22 Zornitza Stark Mode of inheritance for gene: PMP22 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4452 PTPA Zornitza Stark Publications for gene: PTPA were set to 36073231; 37448355
Mendeliome v1.4451 PTPA Zornitza Stark edited their review of gene: PTPA: Added comment: Further family reported in PMID 37046398 with homozygous missense and early onset PD; however, variant is hmz missense with no supportive data.; Changed publications: 36073231, 37046398
Mendeliome v1.4451 NEK9 Zornitza Stark Publications for gene: NEK9 were set to 26908619; 21271645
Mendeliome v1.4450 NEK9 Zornitza Stark Classified gene: NEK9 as Green List (high evidence)
Mendeliome v1.4450 NEK9 Zornitza Stark Gene: nek9 has been classified as Green List (High Evidence).
Mendeliome v1.4449 NEK9 Zornitza Stark edited their review of gene: NEK9: Added comment: PMID 36712877: 2 more families reported with neonatal arthrogryposis, contractures, camptodactyly, atrial septal defect, mild pulmonary stenosis, and pyloric stenosis; biallelic LoF variants.; Changed rating: GREEN; Changed publications: 26908619, 21271645, 36712877
Mendeliome v1.4449 NDNF Zornitza Stark Publications for gene: NDNF were set to 31883645; 40788466
Mendeliome v1.4448 NDNF Zornitza Stark Mode of inheritance for gene: NDNF was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4447 NDNF Zornitza Stark edited their review of gene: NDNF: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4447 NDNF Zornitza Stark edited their review of gene: NDNF: Added comment: PMID 36454653: another individual with homozygous LoF variant and Kallman syndrome.; Changed publications: 31883645, 40788466, 36454653; Changed phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841
Mendeliome v1.4447 NAV2 Zornitza Stark Phenotypes for gene: NAV2 were changed from Developmental delay; cerebellar hypoplasia; cerebellar dysplasia to Neurodevelopmental disorder, MONDO:0700092, NAV2-related
Mendeliome v1.4446 NAV2 Zornitza Stark reviewed gene: NAV2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NAV2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4446 RSF1 Rylee Peters Marked gene: RSF1 as ready
Mendeliome v1.4446 RSF1 Rylee Peters Gene: rsf1 has been classified as Green List (High Evidence).
Mendeliome v1.4446 PMP22 Sangavi Sivagnanasundram reviewed gene: PMP22: Rating: GREEN; Mode of pathogenicity: None; Publications: 32412171, 31777123, 32719652; Phenotypes: Charcot-Marie-Tooth disease type 3 MONDO:0007790, Charcot-Marie-Tooth disease type 1A MONDO:0007309, hereditary neuropathy with liability to pressure palsies MONDO:0008087; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4446 LRRC32 Zornitza Stark Publications for gene: LRRC32 were set to 30976112
Mendeliome v1.4445 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Added comment: Further family reported in PMID 41041957, homozygous missense variant.; Changed publications: 30976112, 41041957
Mendeliome v1.4445 MIR204 Zornitza Stark Publications for gene: MIR204 were set to 26056285; 37321975
Mendeliome v1.4444 MIR204 Zornitza Stark Classified gene: MIR204 as Green List (high evidence)
Mendeliome v1.4444 MIR204 Zornitza Stark Gene: mir204 has been classified as Green List (High Evidence).
Mendeliome v1.4443 MIR204 Zornitza Stark changed review comment from: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development.

Mouse model in PMID 31332443 recapitulates retinal phenotype.; to: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development.

Mouse model in PMID 31332443 recapitulates retinal phenotype.

MODERATE by ClinGen.
Mendeliome v1.4443 MIR204 Zornitza Stark changed review comment from: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development; to: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development.

Mouse model in PMID 31332443 recapitulates retinal phenotype.
Mendeliome v1.4443 MIR204 Zornitza Stark edited their review of gene: MIR204: Changed publications: 38867642, 20713703, 31332443
Mendeliome v1.4443 MIR204 Zornitza Stark edited their review of gene: MIR204: Changed publications: 38867642, 20713703
Mendeliome v1.4443 MIR204 Zornitza Stark changed review comment from: Two families only; to: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development
Mendeliome v1.4443 MIR204 Zornitza Stark edited their review of gene: MIR204: Changed rating: GREEN; Changed publications: 38867642; Changed phenotypes: Retinal dystrophy and iris coloboma with or without cataract (MIM#616722); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4443 MIR204 Zornitza Stark reviewed gene: MIR204: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.4443 RSF1 Rylee Peters Classified gene: RSF1 as Green List (high evidence)
Mendeliome v1.4443 RSF1 Rylee Peters Gene: rsf1 has been classified as Green List (High Evidence).
Mendeliome v1.4442 RSF1 Rylee Peters gene: RSF1 was added
gene: RSF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RSF1 were set to 41606215
Phenotypes for gene: RSF1 were set to Neurodevelopmental disorder, MONDO:0700092, RSF1-related
Review for gene: RSF1 was set to GREEN
Added comment: PMID: 41606215 describes 11 individuals from 11 unrelated families with heterozygous RSF1 variants causing a syndromic neurodevelopmental disorder with intellectual disability or limit scores (7/11), ASD (4/11) and developmental delay (6/11). Other features described include dysmorphism (5/7), variable macro‑/microcephaly (3/6), epilepsy (2/7), and brain MRI anomalies (2/4). Majority of the variants are de novo, one was inherited from a mosaic mother and another inherited from an affected father.
Sources: Literature
Mendeliome v1.4441 GINS3 Zornitza Stark Phenotypes for gene: GINS3 were changed from Meier-Gorlin syndrome, MONDO:0016817, GINS3-related to Meier-Gorlin syndrome 9, MIM# 621512
Mendeliome v1.4440 GINS3 Zornitza Stark edited their review of gene: GINS3: Changed phenotypes: Meier-Gorlin syndrome 9, MIM# 621512
Mendeliome v1.4440 CFAP70 Bryony Thompson gene: CFAP70 was added
gene: CFAP70 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP70 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP70 were set to 31621862
Phenotypes for gene: CFAP70 were set to spermatogenic failure MONDO:0004983
Review for gene: CFAP70 was set to RED
Added comment: A single case reported.
Sources: Literature
Mendeliome v1.4439 QRICH2 Bryony Thompson Classified gene: QRICH2 as Green List (high evidence)
Mendeliome v1.4439 QRICH2 Bryony Thompson Gene: qrich2 has been classified as Green List (High Evidence).
Mendeliome v1.4438 QRICH2 Bryony Thompson gene: QRICH2 was added
gene: QRICH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: QRICH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QRICH2 were set to 30683861; 31292949
Phenotypes for gene: QRICH2 were set to spermatogenic failure MONDO:0004983
Review for gene: QRICH2 was set to GREEN
Added comment: At least 4 unrelated men and a supporting mouse model.
Sources: Literature
Mendeliome v1.4437 TMTC4 Bryony Thompson gene: TMTC4 was added
gene: TMTC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMTC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMTC4 were set to 37943620
Phenotypes for gene: TMTC4 were set to hearing loss, autosomal recessive MONDO:0019588
Review for gene: TMTC4 was set to RED
Added comment: A single family reported and a supporting mouse model
Sources: Literature
Mendeliome v1.4436 WDR66 Bryony Thompson Classified gene: WDR66 as Green List (high evidence)
Mendeliome v1.4436 WDR66 Bryony Thompson Gene: wdr66 has been classified as Green List (High Evidence).
Mendeliome v1.4435 WDR66 Bryony Thompson gene: WDR66 was added
gene: WDR66 was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: WDR66.
Mode of inheritance for gene: WDR66 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR66 were set to 30122540; 30122541
Phenotypes for gene: WDR66 were set to spermatogenic failure MONDO:0004983
Review for gene: WDR66 was set to GREEN
Added comment: At least 10 families/men reported.
Sources: Literature
Mendeliome v1.4434 TUBA3D Bryony Thompson Classified gene: TUBA3D as Amber List (moderate evidence)
Mendeliome v1.4434 TUBA3D Bryony Thompson Gene: tuba3d has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4433 TUBA3D Bryony Thompson gene: TUBA3D was added
gene: TUBA3D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUBA3D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA3D were set to 29051577
Phenotypes for gene: TUBA3D were set to keratoconus MONDO:0015486
Review for gene: TUBA3D was set to AMBER
Added comment: 4 cases (including twins) with 2 variants. Functional analysis showed that the mutant proteins led to higher expression of matrix metalloproteinase genes and higher levels of oxidative stress, which the authors suggested would reduce extracellular matrix in the corneas and contribute to stromal thinning.
Sources: Literature
Mendeliome v1.4432 ZFHX2 Bryony Thompson gene: ZFHX2 was added
gene: ZFHX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX2 were set to 29253101
Phenotypes for gene: ZFHX2 were set to congenital insensitivity to pain syndrome, Marsili type MONDO:0958106
Review for gene: ZFHX2 was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Mendeliome v1.4431 CFAP44 Bryony Thompson Classified gene: CFAP44 as Green List (high evidence)
Mendeliome v1.4431 CFAP44 Bryony Thompson Gene: cfap44 has been classified as Green List (High Evidence).
Mendeliome v1.4430 CFAP44 Bryony Thompson gene: CFAP44 was added
gene: CFAP44 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP44 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP44 were set to 28552195; 29277146; 29449551
Phenotypes for gene: CFAP44 were set to spermatogenic failure MONDO:0004983
Review for gene: CFAP44 was set to GREEN
Added comment: At least 11 men reported with biallelic variants and a supporting mouse model.
Sources: Literature
Mendeliome v1.4429 CLPX Bryony Thompson gene: CLPX was added
gene: CLPX was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLPX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLPX were set to 28874591; 25957689
Phenotypes for gene: CLPX were set to protoporphyria, erythropoietic, 2 MONDO:0060729
Review for gene: CLPX was set to RED
Added comment: A single family reported and a supporting zebrafish model.
Sources: Literature
Mendeliome v1.4428 AK7 Bryony Thompson reviewed gene: AK7: Rating: RED; Mode of pathogenicity: None; Publications: 29365104; Phenotypes: spermatogenic failure MONDO:0004983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4428 AK9 Bryony Thompson Classified gene: AK9 as Green List (high evidence)
Mendeliome v1.4428 AK9 Bryony Thompson Gene: ak9 has been classified as Green List (High Evidence).
Mendeliome v1.4427 AK9 Bryony Thompson gene: AK9 was added
gene: AK9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AK9 were set to 37713809
Phenotypes for gene: AK9 were set to spermatogenic failure MONDO:0004983
Review for gene: AK9 was set to GREEN
Added comment: At least 5 unrelated men and a supporting mouse model.
Sources: Literature
Mendeliome v1.4426 EXOC8 Bryony Thompson Classified gene: EXOC8 as Green List (high evidence)
Mendeliome v1.4426 EXOC8 Bryony Thompson Gene: exoc8 has been classified as Green List (High Evidence).
Mendeliome v1.4425 EXOC8 Bryony Thompson gene: EXOC8 was added
gene: EXOC8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC8 were set to 32103185; 22700954; 36344539; 35460391
Phenotypes for gene: EXOC8 were set to neurodevelopmental disorder with microcephaly, seizures, and brain atrophy MONDO:0033662
Review for gene: EXOC8 was set to GREEN
Added comment: At least 4 families/cases with a neurodevelopmental phenotype.
Sources: Literature
Mendeliome v1.4424 TUBB6 Bryony Thompson gene: TUBB6 was added
gene: TUBB6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUBB6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB6 were set to 29016863
Phenotypes for gene: TUBB6 were set to facial palsy, congenital, with ptosis and velopharyngeal dysfunction MONDO:0060589
Review for gene: TUBB6 was set to RED
Added comment: A single family reported.
Sources: Literature
Mendeliome v1.4423 EPS8L3 Bryony Thompson gene: EPS8L3 was added
gene: EPS8L3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EPS8L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPS8L3 were set to 23099647
Phenotypes for gene: EPS8L3 were set to Marie Unna hereditary hypotrichosis MONDO:0018631
Review for gene: EPS8L3 was set to RED
Added comment: A single family reported.
Sources: Literature
Mendeliome v1.4422 MIR2861 Bryony Thompson gene: MIR2861 was added
gene: MIR2861 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MIR2861 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MIR2861 were set to 19920351
Phenotypes for gene: MIR2861 were set to osteoporosis MONDO:0005298
Review for gene: MIR2861 was set to RED
Added comment: A single family reported.
Sources: Literature
Mendeliome v1.4421 AVIL Bryony Thompson Classified gene: AVIL as Green List (high evidence)
Mendeliome v1.4421 AVIL Bryony Thompson Gene: avil has been classified as Green List (High Evidence).
Mendeliome v1.4420 AVIL Bryony Thompson gene: AVIL was added
gene: AVIL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AVIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AVIL were set to 29058690
Phenotypes for gene: AVIL were set to Nephrotic syndrome, type 21 MONDO:0032826
Review for gene: AVIL was set to GREEN
Added comment: 3 cases with 4 different variants and supporting in vitro functional assays demonstrating that the variants altered podocyte migration.
Sources: Literature
Mendeliome v1.4419 SPACA1 Bryony Thompson gene: SPACA1 was added
gene: SPACA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPACA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPACA1 were set to 34172998; 22949614
Phenotypes for gene: SPACA1 were set to spermatogenic failure MONDO:0004983
Review for gene: SPACA1 was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Mendeliome v1.4418 ABCA5 Bryony Thompson gene: ABCA5 was added
gene: ABCA5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ABCA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA5 were set to 24831815
Phenotypes for gene: ABCA5 were set to gingival fibromatosis-hypertrichosis syndrome MONDO:0007610
Review for gene: ABCA5 was set to RED
Added comment: A single case was reported, and a supporting mouse model
Sources: Literature
Mendeliome v1.4417 TRIM44 Bryony Thompson Marked gene: TRIM44 as ready
Mendeliome v1.4417 TRIM44 Bryony Thompson Gene: trim44 has been classified as Red List (Low Evidence).
Mendeliome v1.4417 TRIM44 Bryony Thompson gene: TRIM44 was added
gene: TRIM44 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM44 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM44 were set to 26394807
Phenotypes for gene: TRIM44 were set to Aniridia 3 MONDO:0014938
Review for gene: TRIM44 was set to RED
Added comment: A single family reported
Sources: Literature
Mendeliome v1.4416 SLC17A9 Bryony Thompson Marked gene: SLC17A9 as ready
Mendeliome v1.4416 SLC17A9 Bryony Thompson Gene: slc17a9 has been classified as Green List (High Evidence).
Mendeliome v1.4416 SLC17A9 Bryony Thompson Classified gene: SLC17A9 as Green List (high evidence)
Mendeliome v1.4416 SLC17A9 Bryony Thompson Gene: slc17a9 has been classified as Green List (High Evidence).
Mendeliome v1.4415 SLC17A9 Bryony Thompson gene: SLC17A9 was added
gene: SLC17A9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC17A9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC17A9 were set to 25180256; 25596766
Phenotypes for gene: SLC17A9 were set to disseminated superficial actinic porokeratosis MONDO:0019212
Review for gene: SLC17A9 was set to GREEN
Added comment: 3 families reported with evidence of segregation with disease.
Sources: Literature
Mendeliome v1.4414 CENPT Bryony Thompson Marked gene: CENPT as ready
Mendeliome v1.4414 CENPT Bryony Thompson Gene: cenpt has been classified as Red List (Low Evidence).
Mendeliome v1.4414 CENPT Bryony Thompson gene: CENPT was added
gene: CENPT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to short stature and microcephaly with genital anomalies MONDO:0032875
Review for gene: CENPT was set to RED
Added comment: A single family reported, and a supporting zebrafish model.
Sources: Literature
Mendeliome v1.4413 BMS1 Bryony Thompson Marked gene: BMS1 as ready
Mendeliome v1.4413 BMS1 Bryony Thompson Gene: bms1 has been classified as Red List (Low Evidence).
Mendeliome v1.4413 BMS1 Bryony Thompson gene: BMS1 was added
gene: BMS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMS1 were set to 23785305
Phenotypes for gene: BMS1 were set to aplasia cutis congenita MONDO:0007145
Review for gene: BMS1 was set to RED
Added comment: A single family reported.
Sources: Literature
Mendeliome v1.4412 TTC21A Bryony Thompson Marked gene: TTC21A as ready
Mendeliome v1.4412 TTC21A Bryony Thompson Gene: ttc21a has been classified as Green List (High Evidence).
Mendeliome v1.4412 TTC21A Bryony Thompson Classified gene: TTC21A as Green List (high evidence)
Mendeliome v1.4412 TTC21A Bryony Thompson Gene: ttc21a has been classified as Green List (High Evidence).
Mendeliome v1.4411 TTC21A Bryony Thompson gene: TTC21A was added
gene: TTC21A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC21A were set to 30929735
Phenotypes for gene: TTC21A were set to spermatogenic failure MONDO:0004983
Review for gene: TTC21A was set to GREEN
Added comment: At least 3 men reported with biallelic variants and a supporting mouse model
Sources: Literature
Mendeliome v1.4410 Bryony Thompson Copied gene DNAL4 from panel Mirror movements
Mendeliome v1.4410 DNAL4 Bryony Thompson gene: DNAL4 was added
gene: DNAL4 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DNAL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAL4 were set to 25098561; 25236653
Phenotypes for gene: DNAL4 were set to Mirror movements 3 MIM#616059
Mendeliome v1.4409 MAATS1 Bryony Thompson Classified gene: MAATS1 as Green List (high evidence)
Mendeliome v1.4409 MAATS1 Bryony Thompson Gene: maats1 has been classified as Green List (High Evidence).
Mendeliome v1.4408 MAATS1 Bryony Thompson gene: MAATS1 was added
gene: MAATS1 was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: MAATS1.
Mode of inheritance for gene: MAATS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAATS1 were set to 32161152
Phenotypes for gene: MAATS1 were set to spermatogenic failure MONDO:0004983
Review for gene: MAATS1 was set to GREEN
Added comment: 6 unrelated men of North African origin homozygous for 2 different variants and a supporting Trypanosoma brucei model.
Sources: Literature
Mendeliome v1.4407 CELA2A Bryony Thompson Classified gene: CELA2A as Green List (high evidence)
Mendeliome v1.4407 CELA2A Bryony Thompson Gene: cela2a has been classified as Green List (High Evidence).
Mendeliome v1.4406 CELA2A Bryony Thompson gene: CELA2A was added
gene: CELA2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CELA2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELA2A were set to 31358993
Phenotypes for gene: CELA2A were set to abdominal obesity-metabolic syndrome 4 MONDO:0032837
Review for gene: CELA2A was set to GREEN
Added comment: 4 families/cases with a combination of the following features obesity, coronary artery disease, hypertriglyceridemia, hypertension, and type 2 diabetes. Segregation evidence in a large family and supporting in vitro fucntional studies.
Sources: Literature
Mendeliome v1.4405 TRIM36 Bryony Thompson gene: TRIM36 was added
gene: TRIM36 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM36 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM36 were set to 28087737
Phenotypes for gene: TRIM36 were set to anencephaly MONDO:0000819
Review for gene: TRIM36 was set to RED
Added comment: A single foetus was reported with a homozygous variant.
Sources: Literature
Mendeliome v1.4404 GREM2 Bryony Thompson Classified gene: GREM2 as Amber List (moderate evidence)
Mendeliome v1.4404 GREM2 Bryony Thompson Gene: grem2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4403 GREM2 Bryony Thompson gene: GREM2 was added
gene: GREM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GREM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREM2 were set to 26416033; 28992378; 24686385
Phenotypes for gene: GREM2 were set to Tooth agenesis, selective, 9 MONDO:0014999
Review for gene: GREM2 was set to AMBER
Added comment: 3 missense variants reported in 8 cases. Incomplete penetrance and variable expressivity were demonstrated. Also, a supporting mouse model.
Sources: Literature
Mendeliome v1.4402 ZPBP Bryony Thompson gene: ZPBP was added
gene: ZPBP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZPBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPBP were set to 31985809; 17664285
Phenotypes for gene: ZPBP were set to spermatogenic failure MONDO:0004983
Review for gene: ZPBP was set to RED
Added comment: A single male case reported with a homozygous variant, and a supporting mouse model.
Sources: Literature
Mendeliome v1.4401 NANOS1 Bryony Thompson Classified gene: NANOS1 as Amber List (moderate evidence)
Mendeliome v1.4401 NANOS1 Bryony Thompson Gene: nanos1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4400 NANOS1 Bryony Thompson gene: NANOS1 was added
gene: NANOS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NANOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NANOS1 were set to 23315541
Phenotypes for gene: NANOS1 were set to spermatogenic failure MONDO:0004983
Review for gene: NANOS1 was set to AMBER
Added comment: 5 men with 3 different non-synonymous variants and incomplete segregation. 2 of the variants are inframe deletions in repeat regions.
Sources: Literature
Mendeliome v1.4399 ARHGEF2 Bryony Thompson gene: ARHGEF2 was added
gene: ARHGEF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGEF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGEF2 were set to 28453519
Phenotypes for gene: ARHGEF2 were set to neurodevelopmental disorder with midbrain and hindbrain malformations MONDO:0056797
Review for gene: ARHGEF2 was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Mendeliome v1.4398 TSGA10 Bryony Thompson gene: TSGA10 was added
gene: TSGA10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TSGA10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSGA10 were set to 28905369
Phenotypes for gene: TSGA10 were set to spermatogenic failure MONDO:0004983
Review for gene: TSGA10 was set to RED
Added comment: A single case reported with a homozygous variant.
Sources: Literature
Mendeliome v1.4397 ELP4 Bryony Thompson Marked gene: ELP4 as ready
Mendeliome v1.4397 ELP4 Bryony Thompson Gene: elp4 has been classified as Green List (High Evidence).
Mendeliome v1.4397 ELP4 Bryony Thompson Classified gene: ELP4 as Green List (high evidence)
Mendeliome v1.4397 ELP4 Bryony Thompson Gene: elp4 has been classified as Green List (High Evidence).
Mendeliome v1.4396 ELP4 Bryony Thompson gene: ELP4 was added
gene: ELP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ELP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELP4 were set to 24290376; 17679951; 22991255; 26010655
Phenotypes for gene: ELP4 were set to ocular dysgenesis caused by defects in PAX6 regulation MONDO:0700246
Mode of pathogenicity for gene: ELP4 was set to Other
Review for gene: ELP4 was set to GREEN
Added comment: At least 5 families/cases reported with ocular dysgenesis. The mechanism of disease appears to be monoallelic disruption of enhancer elements located in the introns of ELP4 but required for efficient PAX6 transactivation during ocular development through a feed-forward mechanism mediated by binding of the PAX6 transcription factor
Sources: Literature
Mendeliome v1.4395 NUP155 Bryony Thompson gene: NUP155 was added
gene: NUP155 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP155 were set to 19070573
Phenotypes for gene: NUP155 were set to familial atrial fibrillation MONDO:0018054
Review for gene: NUP155 was set to RED
Added comment: A single family reported and a supporting mouse model
Sources: Literature
Mendeliome v1.4394 HDAC9 Bryony Thompson gene: HDAC9 was added
gene: HDAC9 was added to Mendeliome. Sources: ClinGen
disputed tags were added to gene: HDAC9.
Mode of inheritance for gene: HDAC9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC9 were set to 34750192; 35710300; 38318288
Phenotypes for gene: HDAC9 were set to Auriculocondylar syndrome MONDO:0000107
Review for gene: HDAC9 was set to RED
Added comment: Disputed classification by Craniofacial Malformations GCEP 20/11/2025
https://search.clinicalgenome.org/CCID:009067
Sources: ClinGen
Mendeliome v1.4393 SLC44A4 Bryony Thompson gene: SLC44A4 was added
gene: SLC44A4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC44A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC44A4 were set to 28013291
Phenotypes for gene: SLC44A4 were set to nonsyndromic genetic hearing loss MONDO:0019497
Review for gene: SLC44A4 was set to RED
Added comment: A single family reported and a supporting zebrafish model.
Sources: Literature
Mendeliome v1.4392 ADGRE2 Bryony Thompson gene: ADGRE2 was added
gene: ADGRE2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGRE2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRE2 were set to 26841242
Phenotypes for gene: ADGRE2 were set to autosomal dominant vibratory urticaria MONDO:0007447
Mode of pathogenicity for gene: ADGRE2 was set to Other
Review for gene: ADGRE2 was set to RED
Added comment: A single family reported segregating a gain-of-function missense variant.
Sources: Literature
Mendeliome v1.4391 Bryony Thompson Added reviews for gene TEX15 from panel Mendeliome
Mendeliome v1.4390 TEX15 Bryony Thompson Marked gene: TEX15 as ready
Mendeliome v1.4390 TEX15 Bryony Thompson Gene: tex15 has been classified as Green List (High Evidence).
Mendeliome v1.4390 TEX15 Bryony Thompson Classified gene: TEX15 as Green List (high evidence)
Mendeliome v1.4390 TEX15 Bryony Thompson Gene: tex15 has been classified as Green List (High Evidence).
Mendeliome v1.4389 TEX15 Bryony Thompson gene: TEX15 was added
gene: TEX15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TEX15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEX15 were set to 26199321; 28355598; 28303806
Phenotypes for gene: TEX15 were set to spermatogenic failure MONDO:0004983
Review for gene: TEX15 was set to GREEN
Added comment: At least 3 families reported with infertile males and a supporting mouse model.
Sources: Literature
Mendeliome v1.4388 SPINK2 Bryony Thompson gene: SPINK2 was added
gene: SPINK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPINK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPINK2 were set to 28554943
Phenotypes for gene: SPINK2 were set to spermatogenic failure MONDO:0004983
Review for gene: SPINK2 was set to RED
Added comment: A single family reported and a supporting null mouse model.
Sources: Literature
Mendeliome v1.4387 CDK4 Zornitza Stark Phenotypes for gene: CDK4 were changed from Neurodevelopmental disorder, MONDO:0700092; {Melanoma, cutaneous malignant, 3} MIM#609048 to Microcephaly 31, primary, autosomal recessive, MIM# 621507; {Melanoma, cutaneous malignant, 3} MIM#609048
Mendeliome v1.4386 CDK4 Zornitza Stark edited their review of gene: CDK4: Changed phenotypes: Microcephaly 31, primary, autosomal recessive, MIM# 621507
Mendeliome v1.4386 AKAP3 Bryony Thompson Classified gene: AKAP3 as Amber List (moderate evidence)
Mendeliome v1.4386 AKAP3 Bryony Thompson Gene: akap3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4385 AKAP3 Bryony Thompson gene: AKAP3 was added
gene: AKAP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AKAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKAP3 were set to 35228300; 31969357
Phenotypes for gene: AKAP3 were set to spermatogenic failure MONDO:0004983
Review for gene: AKAP3 was set to AMBER
Added comment: 2 unrelated males from consanguineous families with homozygous variants (frameshift, missense), and supporting mouse model.
Sources: Literature
Mendeliome v1.4384 GAB1 Bryony Thompson gene: GAB1 was added
gene: GAB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAB1 were set to 29408807
Phenotypes for gene: GAB1 were set to hearing loss, autosomal recessive MONDO:0019588
Review for gene: GAB1 was set to RED
Added comment: A single family reported.
Sources: Literature
Mendeliome v1.4383 TIMELESS Bryony Thompson Marked gene: TIMELESS as ready
Mendeliome v1.4383 TIMELESS Bryony Thompson Gene: timeless has been classified as Red List (Low Evidence).
Mendeliome v1.4383 TIMELESS Bryony Thompson gene: TIMELESS was added
gene: TIMELESS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TIMELESS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TIMELESS were set to 31138685
Phenotypes for gene: TIMELESS were set to Advance sleep phase syndrome MONDO:0015609
Review for gene: TIMELESS was set to RED
Added comment: A single family reported, and a supporting mouse model
Sources: Literature
Mendeliome v1.4382 Bryony Thompson Copied gene RPL21 from panel Hair disorders
Mendeliome v1.4382 RPL21 Bryony Thompson gene: RPL21 was added
gene: RPL21 was added to Mendeliome. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: RPL21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL21 were set to 21412954
Phenotypes for gene: RPL21 were set to Hypotrichosis 12 MIM#615885
Mendeliome v1.4381 IGSF3 Bryony Thompson gene: IGSF3 was added
gene: IGSF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IGSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGSF3 were set to 24372406
Phenotypes for gene: IGSF3 were set to familial congenital nasolacrimal duct obstruction MONDO:0007871
Review for gene: IGSF3 was set to RED
Added comment: A single consanguineous family reported with a homozygous variant.
Sources: Literature
Mendeliome v1.4380 PER3 Bryony Thompson gene: PER3 was added
gene: PER3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PER3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PER3 were set to 26903630
Phenotypes for gene: PER3 were set to advanced sleep phase syndrome MONDO:0015609
Review for gene: PER3 was set to RED
Added comment: A haplotype (P415A and H417R) segregating in a single family and common in gnomAD (0.5%).
Sources: Literature
Mendeliome v1.4379 PDE1C Bryony Thompson gene: PDE1C was added
gene: PDE1C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDE1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE1C were set to 29860631
Phenotypes for gene: PDE1C were set to autosomal dominant nonsyndromic hearing loss MONDO:0019587
Review for gene: PDE1C was set to RED
Added comment: A single family reported.
Sources: Literature
Mendeliome v1.4378 PI4KB Bryony Thompson Classified gene: PI4KB as Green List (high evidence)
Mendeliome v1.4378 PI4KB Bryony Thompson Gene: pi4kb has been classified as Green List (High Evidence).
Mendeliome v1.4377 PI4KB Bryony Thompson gene: PI4KB was added
gene: PI4KB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PI4KB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PI4KB were set to 33358777
Phenotypes for gene: PI4KB were set to hearing loss, autosomal dominant 87 MONDO:0859525
Review for gene: PI4KB was set to GREEN
Added comment: A missense variant (p.Gln121Arg) segregating in a family and 3 other missense variants (p.Val434Gly, p.Glu667Lys, p.Met739Arg) were identified in 5 unrelated "sporadic" cases. All 4 missense variants were overexpressed in zebrafish embryos, resulting in impaired hearing function, and a null zebrafish model had inner ear abnormalities and audiosensory impairment. Missense showed to have dominant negative effects.
Sources: Literature
Mendeliome v1.4376 MARK3 Bryony Thompson Marked gene: MARK3 as ready
Mendeliome v1.4376 MARK3 Bryony Thompson Gene: mark3 has been classified as Red List (Low Evidence).
Mendeliome v1.4376 MARK3 Bryony Thompson gene: MARK3 was added
gene: MARK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MARK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARK3 were set to 29771303
Phenotypes for gene: MARK3 were set to visual impairment and progressive phthisis bulbi MONDO:0032655
Review for gene: MARK3 was set to RED
Added comment: A single consanguineous family with a homozygous variant and a supporting drosphila model.
Sources: Literature
Mendeliome v1.4375 NRIP1 Bryony Thompson Marked gene: NRIP1 as ready
Mendeliome v1.4375 NRIP1 Bryony Thompson Gene: nrip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4375 NRIP1 Bryony Thompson Classified gene: NRIP1 as Amber List (moderate evidence)
Mendeliome v1.4375 NRIP1 Bryony Thompson Gene: nrip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4374 NRIP1 Bryony Thompson gene: NRIP1 was added
gene: NRIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRIP1 were set to 28381549; 34525250
Phenotypes for gene: NRIP1 were set to congenital anomalies of kidney and urinary tract 3 MONDO:0032646
Review for gene: NRIP1 was set to AMBER
Added comment: 2 families segregating 2 different truncating variants, with incomplete penetrance (1 unaffected carrier). Also, a supporting mouse model. Another case reported with a missense variant inherited from the unaffected mother.
Sources: Literature
Mendeliome v1.4373 Bryony Thompson Copied gene SALL2 from panel Anophthalmia_Microphthalmia_Coloboma
Mendeliome v1.4373 SALL2 Bryony Thompson gene: SALL2 was added
gene: SALL2 was added to Mendeliome. Sources: Expert Review Red,Other
Mode of inheritance for gene: SALL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SALL2 were set to 24412933
Phenotypes for gene: SALL2 were set to Coloboma, ocular, autosomal recessive, MIM#16820
Mendeliome v1.4372 BRDT Bryony Thompson Marked gene: BRDT as ready
Mendeliome v1.4372 BRDT Bryony Thompson Gene: brdt has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4372 BRDT Bryony Thompson Classified gene: BRDT as Amber List (moderate evidence)
Mendeliome v1.4372 BRDT Bryony Thompson Gene: brdt has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4371 BRDT Bryony Thompson gene: BRDT was added
gene: BRDT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BRDT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRDT were set to 32469048; 28199965; 22922464
Phenotypes for gene: BRDT were set to Spermatogenic failure MONDO:0004983
Review for gene: BRDT was set to AMBER
Added comment: 2 cases with 2 different homozygous missense (one with a suggestive gain-of-function mechanism - G928D). A null mouse model had meiotic arrest of spermatogenesis.
Sources: Literature
Mendeliome v1.4370 MAPKAPK3 Bryony Thompson gene: MAPKAPK3 was added
gene: MAPKAPK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAPKAPK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPKAPK3 were set to 26744326
Phenotypes for gene: MAPKAPK3 were set to patterned macular dystrophy 3 MONDO:0014920
Review for gene: MAPKAPK3 was set to RED
Added comment: A single family reported, and a supporting mouse model
Sources: Literature
Mendeliome v1.4369 TAF4B Bryony Thompson gene: TAF4B was added
gene: TAF4B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TAF4B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF4B were set to 24431330; 15774719
Phenotypes for gene: TAF4B were set to spermatogenic failure MONDO:0004983
Review for gene: TAF4B was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Mendeliome v1.4368 CRYBA2 Bryony Thompson Marked gene: CRYBA2 as ready
Mendeliome v1.4368 CRYBA2 Bryony Thompson Gene: cryba2 has been classified as Green List (High Evidence).
Mendeliome v1.4368 CRYBA2 Bryony Thompson Classified gene: CRYBA2 as Green List (high evidence)
Mendeliome v1.4368 CRYBA2 Bryony Thompson Gene: cryba2 has been classified as Green List (High Evidence).
Mendeliome v1.4367 CRYBA2 Bryony Thompson gene: CRYBA2 was added
gene: CRYBA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRYBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYBA2 were set to 23508780; 37438446; 21212184; 38909969; 34014271; 28450710
Phenotypes for gene: CRYBA2 were set to cataract MONDO:0005129
Review for gene: CRYBA2 was set to GREEN
Added comment: 5 reported families/cases with missense variants, 3 families segregating variants with incomplete penetrance. Also, a supporting mouse model
Sources: Literature
Mendeliome v1.4366 Bryony Thompson Copied gene MMP14 from panel Skeletal dysplasia
Mendeliome v1.4366 MMP14 Bryony Thompson gene: MMP14 was added
gene: MMP14 was added to Mendeliome. Sources: Expert Review Amber
Mode of inheritance for gene: MMP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMP14 were set to 29741626; 22922033; 10520996
Phenotypes for gene: MMP14 were set to Winchester syndrome 277950
Mendeliome v1.4365 P4HA2 Bryony Thompson Classified gene: P4HA2 as Green List (high evidence)
Mendeliome v1.4365 P4HA2 Bryony Thompson Gene: p4ha2 has been classified as Green List (High Evidence).
Mendeliome v1.4364 P4HA2 Bryony Thompson gene: P4HA2 was added
gene: P4HA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: P4HA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: P4HA2 were set to 25741866
Phenotypes for gene: P4HA2 were set to myopia MONDO:0001384
Review for gene: P4HA2 was set to GREEN
Added comment: At least 6 families reported with nonsyndromic myopia.
Sources: Literature
Mendeliome v1.4363 ITPR2 Bryony Thompson Marked gene: ITPR2 as ready
Mendeliome v1.4363 ITPR2 Bryony Thompson Gene: itpr2 has been classified as Red List (Low Evidence).
Mendeliome v1.4363 ITPR2 Bryony Thompson gene: ITPR2 was added
gene: ITPR2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPR2 were set to 25329695
Phenotypes for gene: ITPR2 were set to isolated anhidrosis with normal sweat glands MONDO:0007118
Review for gene: ITPR2 was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Mendeliome v1.4362 SSX1 Bryony Thompson Marked gene: SSX1 as ready
Mendeliome v1.4362 SSX1 Bryony Thompson Gene: ssx1 has been classified as Green List (High Evidence).
Mendeliome v1.4362 SSX1 Bryony Thompson Classified gene: SSX1 as Green List (high evidence)
Mendeliome v1.4362 SSX1 Bryony Thompson Gene: ssx1 has been classified as Green List (High Evidence).
Mendeliome v1.4361 SSX1 Bryony Thompson gene: SSX1 was added
gene: SSX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SSX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SSX1 were set to 36796361
Phenotypes for gene: SSX1 were set to spermatogenic failure, X-linked, 5 MONDO:085947
Review for gene: SSX1 was set to GREEN
Added comment: At least 6 unrelated men with hemizygous variants and a supporting mouse model.
Sources: Literature
Mendeliome v1.4360 CT55 Bryony Thompson gene: CT55 was added
gene: CT55 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CT55 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CT55 were set to 36481789
Phenotypes for gene: CT55 were set to Spermatogenic failure MONDO:0004983
Review for gene: CT55 was set to RED
Added comment: 2 Chinese brothers with infertility, hemizygous for a nonsense variant and supporting mouse model.
Sources: Literature
Mendeliome v1.4359 GPRASP2 Bryony Thompson Marked gene: GPRASP2 as ready
Mendeliome v1.4359 GPRASP2 Bryony Thompson Gene: gprasp2 has been classified as Red List (Low Evidence).
Mendeliome v1.4359 GPRASP2 Bryony Thompson gene: GPRASP2 was added
gene: GPRASP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPRASP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPRASP2 were set to 28096187; 41688572
Phenotypes for gene: GPRASP2 were set to X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome MONDO:0044702
Review for gene: GPRASP2 was set to RED
Added comment: A single family reported segregating a hemizygous delins with deafness and a supporting deficient mouse model.
Sources: Literature
Mendeliome v1.4358 ADGRG2 Bryony Thompson Marked gene: ADGRG2 as ready
Mendeliome v1.4358 ADGRG2 Bryony Thompson Gene: adgrg2 has been classified as Green List (High Evidence).
Mendeliome v1.4358 ADGRG2 Bryony Thompson Classified gene: ADGRG2 as Green List (high evidence)
Mendeliome v1.4358 ADGRG2 Bryony Thompson Gene: adgrg2 has been classified as Green List (High Evidence).
Mendeliome v1.4357 ADGRG2 Bryony Thompson gene: ADGRG2 was added
gene: ADGRG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGRG2 was set to Other
Publications for gene: ADGRG2 were set to 15367682; 27476656
Phenotypes for gene: ADGRG2 were set to congenital bilateral absence of vas deferens MONDO:0018801
Review for gene: ADGRG2 was set to GREEN
Added comment: At least 4 men reported with hemizygous LoF variants and CBAVD. Supporting mouse model. The gene appears to have no biological relevance in women.
Sources: Literature
Mendeliome v1.4356 INSL3 Zornitza Stark Phenotypes for gene: INSL3 were changed from Cryptorchidism, MIM# 219050 to Cryptorchidism, MIM# 219050; Infertility disorder MONDO:0005047, INSL3-related
Mendeliome v1.4355 INSL3 Zornitza Stark Publications for gene: INSL3 were set to 12601553; 12970298; 11095425
Mendeliome v1.4354 INSL3 Zornitza Stark Mode of inheritance for gene: INSL3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4353 INSL3 Zornitza Stark Classified gene: INSL3 as Green List (high evidence)
Mendeliome v1.4353 INSL3 Zornitza Stark Gene: insl3 has been classified as Green List (High Evidence).
Mendeliome v1.4352 INSL3 Zornitza Stark changed review comment from: Note some of the reported variants have relatively high population frequencies in gnomad, unclear if this is monogenic.; to: Initial association reported for mono-allelic variants: Note some of the reported variants have relatively high population frequencies in gnomad, unclear if this is monogenic.
Mendeliome v1.4352 INSL3 Zornitza Stark edited their review of gene: INSL3: Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4352 INSL3 Zornitza Stark edited their review of gene: INSL3: Added comment: PMID 33095795 reports a single individual with a homozygous missense variant c.52G>A p.V18M. Mouse knock‑out studies showed disrupted female cycles and reduced litter size; Changed publications: 12601553, 12970298, 11095425, 41369823, 37208861, 33095795; Changed phenotypes: Cryptorchidism, MIM# 219050, Infertility disorder MONDO:0005047, INSL3-related
Mendeliome v1.4352 INSL3 Zornitza Stark edited their review of gene: INSL3: Added comment: PMID 37208861 reports a single individual with a homozygous frameshift loss‑of‑function variant c.143dupG (p.Arg50Profs*16) presenting with bilateral cryptorchidism diagnosed at birth, early orchidopexy, severe male infertility (non‑obstructive azoospermia, Sertoli‑cell‑only phenotype) and additional features (hypertonia, severe hearing loss, red‑green visual impairment). Functional impact demonstrated by absent INSL3 immunostaining in Leydig cells and undetectable serum INSL3 levels. Additional phenotypic features unlikely explained by INSL3 variant.; Changed publications: 12601553, 12970298, 11095425, 41369823, 37208861
Mendeliome v1.4352 INSL3 Zornitza Stark edited their review of gene: INSL3: Added comment: PMID 41369823 reports two unrelated Chinese Han individuals with homozygous frameshift INSL3 variants presenting with bilateral cryptorchidism, testicular atrophy, azoospermia and elevated FSH/LH. Functional assays (Western blot, immunofluorescence, Co‑IP) showed truncated proteins and loss of RXFP2 interaction; structural modelling predicted abnormal protein conformation; Changed publications: 12601553, 12970298, 11095425, 41369823
Mendeliome v1.4352 IGSF10 Zornitza Stark Publications for gene: IGSF10 were set to 27137492; 31042289; 40700020
Mendeliome v1.4351 IGSF10 Zornitza Stark Mode of inheritance for gene: IGSF10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4350 IGSF10 Zornitza Stark edited their review of gene: IGSF10: Added comment: PMID 31200363: two individuals from unrelated families with bi-allelic variants and hypogonadotropic hypogonadism.
PMID 33208564: single individual with mono-allelic LoF variant and hypogonadotropic hypogonadism.

Still a mixture of MOIs reported, little supportive data, some of the variants postulated to be associated with dominant disease have high pop frequencies.; Changed publications: 27137492, 31042289, 40700020, 31200363, 33208564
Mendeliome v1.4350 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from Vici syndrome, MIM# 242840 to Vici syndrome, MIM# 242840; Neurodevelopmental disorder with parkinsonism or other movement abnormalities, MIM# 621506
Mendeliome v1.4349 EPG5 Zornitza Stark Publications for gene: EPG5 were set to 23222957; 26917586
Mendeliome v1.4348 EPG5 Zornitza Stark edited their review of gene: EPG5: Added comment: Neurodevelopmental disorder with parkinsonism or other movement abnormalities (NEDPAM) is an autosomal recessive disorder characterized by mild to severe developmental delay or intellectual disability and movement abnormalities including spasticity, early onset-parkinsonism with dystonia, myoclonus, or a combination of these. Movement abnormalities may have onset from birth to adulthood in the sixth decade of life. Adolescent-onset dystonia and parkinsonism on the background of neurodevelopmental delay may be rapidly progressive, with cognitive decline. Patients may have additional features such as seizures and optic nerve atrophy.

PMIDs 41053928, 36410285 and 40192014 report over 100 affected individuals.; Changed publications: 23222957, 26917586, 41053928, 36410285, 40192014; Changed phenotypes: Vici syndrome, MIM# 242840, Neurodevelopmental disorder with parkinsonism or other movement abnormalities, MIM# 621506
Mendeliome v1.4348 HNRNPR Lucy Spencer Mode of inheritance for gene: HNRNPR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4347 HNRNPR Lucy Spencer Publications for gene: HNRNPR were set to 26795593; 31079900
Mendeliome v1.4346 HNRNPR Lucy Spencer Phenotypes for gene: HNRNPR were changed from Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, MIM# 620073 to Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, MIM#620073; Spermatogenic failure (MONDO:0004983), HNRNPR-related
Mendeliome v1.4345 HNRNPR Lucy Spencer reviewed gene: HNRNPR: Rating: AMBER; Mode of pathogenicity: None; Publications: 41618099; Phenotypes: Spermatogenic failure (MONDO:0004983), HNRNPR-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4345 SSR3 Sarah Milton reviewed gene: SSR3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32332102; Phenotypes: Congenital disorder of glycosylation, MONDO:0015286, SSR3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4345 NLGN3 Lucy Spencer Phenotypes for gene: NLGN3 were changed from X-linked complex neurodevelopmental disorder MONDO:0100148; {Asperger syndrome susceptibility, X-linked 1} - MIM#300494; {Autism susceptibility, X-linked 1} - MIM#300425 to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425
Mendeliome v1.4344 CCDC141 Zornitza Stark Phenotypes for gene: CCDC141 were changed from Anosmic hypogonadotropic hypogonadism to congenital hypogonadotropic hypogonadism, MONDO:0015770, CCDC141-related
Mendeliome v1.4343 CCDC141 Zornitza Stark Mode of inheritance for gene: CCDC141 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4342 ADCY3 Zornitza Stark Publications for gene: ADCY3 were set to 11055432; 29311636; 29311637
Mendeliome v1.4341 ADCY3 Zornitza Stark Classified gene: ADCY3 as Green List (high evidence)
Mendeliome v1.4341 ADCY3 Zornitza Stark Gene: adcy3 has been classified as Green List (High Evidence).
Mendeliome v1.4340 ADCY3 Zornitza Stark reviewed gene: ADCY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 39519366; Phenotypes: {Obesity, susceptibility to, BMIQ19} MIM#617885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4340 PITX2 upstream regulatory region Sarah Milton Region: PITX2 upstream regulatory region was added
Region: PITX2 upstream regulatory region was added to Mendeliome. Sources: Literature
SV/CNV tags were added to Region: PITX2 upstream regulatory region.
Mode of inheritance for Region: PITX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: PITX2 upstream regulatory region were set to PMID: 20881290, 28911203, 14991915, 9480756
Phenotypes for Region: PITX2 upstream regulatory region were set to Axenfeld-Rieger syndrome, MONDO:0019187
Review for Region: PITX2 upstream regulatory region was set to GREEN
Added comment: PITX2 encodes a homeodomain containing transcription factor.

There have been over 5 affected individuals across a number of publications with deletions in an agenic region approx 150kb upstream of PITX2 presenting with an Axenfeld Rieger phenotype.
There have also been reports of individuals with balanced translocations transecting the region on 4p with a similar phenotype.

Functional studies have interrogated this region identifying 11 conserved elements that are thought to represent enhancers. Zebrafish studies were performed by Volkmann et al with varying sized deletions in the region showing an effect on PITX2 gene expression.
Protas et al used a zebrafish model modified by CRISPR/Cas9 to delete an orthologous region similar to that seen in an affected individual. This resulted in recapitulation of the phenotype.

Note coordinates may not be precise (smaller deletions have been reported to cause disease).
Sources: Literature
Mendeliome v1.4339 FGD5 Krithika Murali Phenotypes for gene: FGD5 were changed from tetralogy of fallot MONDO:0008542 to Congenital heart disease - MONDO:0005453, FGD5-related
Mendeliome v1.4338 FGD5 Krithika Murali Publications for gene: FGD5 were set to 32037394; 30232381
Mendeliome v1.4337 FGD5 Krithika Murali Classified gene: FGD5 as Amber List (moderate evidence)
Mendeliome v1.4337 FGD5 Krithika Murali Gene: fgd5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4336 FGD5 Krithika Murali reviewed gene: FGD5: Rating: AMBER; Mode of pathogenicity: None; Publications: 41574350, 41199744, 32037394, 30232381; Phenotypes: Congenital heart disease - MONDO:0005453, FGD5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4336 RNF213 Michelle Torres changed review comment from: The well-know East Asian founder variant, p.(Arg4810Lys) (aka p.(Arg4859Lys)), has been reported in multiple homozygous individuals with moyamoya disease. In a Japanese cohort, homozygous individuals had a significantly earlier age at onset compared with heterozygotes (PMID: 22377813).

The evidence for AR as a MOI in association with other variants is not convincing (PMIDs: 30922903, 33960657).; to: The well-know East Asian founder variant, p.(Arg4810Lys) (aka p.(Arg4859Lys)), has been reported in multiple homozygous individuals with moyamoya disease. In a Japanese cohort, homozygous individuals had a significantly earlier age at onset compared with heterozygotes (PMID: 22377813).

The evidence for AR as a MOI in association with other variants is not convincing (PMIDs: 30922903, 33960657).

*Specific MONDO for this gene is Moyamoya disease 2 (MONDO:0011784).
Mendeliome v1.4336 RNF213 Michelle Torres reviewed gene: RNF213: Rating: GREEN; Mode of pathogenicity: None; Publications: 22377813, 30922903, 33960657; Phenotypes: Moyamoya disease 2, susceptibility to MIM#607151; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.4336 NME5 Lucy Spencer Phenotypes for gene: NME5 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 48, without situs inversus MIM#620032
Mendeliome v1.4335 NME5 Lucy Spencer Publications for gene: NME5 were set to 32185794
Mendeliome v1.4334 NME5 Lucy Spencer Classified gene: NME5 as Green List (high evidence)
Mendeliome v1.4334 NME5 Lucy Spencer Gene: nme5 has been classified as Green List (High Evidence).
Mendeliome v1.4333 NME5 Lucy Spencer reviewed gene: NME5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32185794, 33635012, 37296588, 37998386, 37957793, 41499646; Phenotypes: Ciliary dyskinesia, primary, 48, without situs inversus MIM#620032; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4333 TBC1D8 Sangavi Sivagnanasundram Classified gene: TBC1D8 as Green List (high evidence)
Mendeliome v1.4333 TBC1D8 Sangavi Sivagnanasundram Gene: tbc1d8 has been classified as Green List (High Evidence).
Mendeliome v1.4332 TBC1D8 Sangavi Sivagnanasundram Classified gene: TBC1D8 as Green List (high evidence)
Mendeliome v1.4332 TBC1D8 Sangavi Sivagnanasundram Gene: tbc1d8 has been classified as Green List (High Evidence).
Mendeliome v1.4331 TBC1D8 Sangavi Sivagnanasundram gene: TBC1D8 was added
gene: TBC1D8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TBC1D8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TBC1D8 were set to 41556581; 35248088; 33584793
Phenotypes for gene: TBC1D8 were set to Lennox‑Gastaut syndrome MONDO:0016532; non-syndromic hearing loss MONDO:0019587; non obstructive azoospermia or cryptozoospermia MONDO:0005372
Review for gene: TBC1D8 was set to GREEN
Added comment: GREEN AR - non-obstructive azoospermia or cryptozoospermia
RED AD - Lennox‑Gastaut syndrome and non-syndromic hearing loss

PMID: 41556581 - Two affected unrelated individuals with biallelic variants
Immunofluorescence staining showed decreased protein expression in the testis of the affected individual compared to that of a fertile individual.

PMID:35248088 - AD non-syndromic hearing loss
De novo heterozygous missense variant in one individual presenting with hearing loss
p.Ser666Leu - GrpMax FAF = 0.2%

PMID: 33584793 - AD Lennox‑Gastaut syndrome
12yrM presented with tonic, atonic seizures however had normal MRI
Assumed de novo missense variant identified
Sources: Literature
Mendeliome v1.4330 ATP11C Lucy Spencer Publications for gene: ATP11C were set to 41523080; 40869043; 37892263; 37671681; 26944472
Mendeliome v1.4329 ATP11C Lucy Spencer edited their review of gene: ATP11C: Changed publications: 41523080, 40869043, 37892263, 37671681, 26944472, 37314652
Mendeliome v1.4329 ATP11C Lucy Spencer changed review comment from: PMID: 40869043 reports 3 unrelated families with haemolytic anaemia and ATP11C variants. Probands were all hemizygous boys who had maternally inherited variants, all variants were absent or only has 1 het in gnomad. One family had a frameshift, another ha 2 missense variants in cis, and the third had a -7 splice variant that RT-PCR showed resulted in an in frame insertion. 2 probands were shown to have normal G6PD activity and haemoglobin, the third was not tested. The proband with the ATP11C frameshift also had a de novo missense in ANK1

PMID: 37892263, 37671681, 26944472 report 3 hemizygous male haemolytic anaemia. However 2 of the patients had pathogenic variants in genes associated with spherocytosis SPTA1 and ANK1. The ATP11C variants were absent or rare in gnomad (note papers use different transcripts/p. numbering to gnomad).

PMID: 41523080 reports 2 of the same patients as PMID:40869043 and additionally looked at Val972Met in a very large cohort of blood donors, but this variant is called Val969Met in gnomad where it has thousands of hets and hemizygotes.
Sources: Literature; to: PMID: 40869043 reports 4 patients from 3 unrelated families with haemolytic anaemia and ATP11C variants. Probands were all hemizygous boys who had maternally inherited variants, all variants were absent or only has 1 het in gnomad. One family had a frameshift, another ha 2 missense variants in cis, and the third had a -7 splice variant that RT-PCR showed resulted in an in frame insertion. 2 probands were shown to have normal G6PD activity and haemoglobin, the third was not tested. The proband with the ATP11C frameshift also had a de novo missense in ANK1. Studies in patient RBS for all 4 patients showed reduced flippase activity.

PMID: 37892263, 37671681, 26944472 report 3 hemizygous male haemolytic anaemia. However 2 of the patients had pathogenic variants in genes associated with spherocytosis SPTA1 and ANK1. The ATP11C variants were absent or rare in gnomad (note papers use different transcripts/p. numbering to gnomad).

PMID: 41523080 reports 2 of the same patients as PMID:40869043 and additionally looked at Val972Met in a very large cohort of blood donors, but this variant is called Val969Met in gnomad where it has thousands of hets and hemizygotes.

PMID: 37314652 One hemizygous male with a frameshift in ATP11C and agranulocytosis, recurrent acute liver failure and developmental delay. Previously published mouse models deficient in ATP11C displayed conjugated hyperbilirubinemia, hyperchloremia, and hemolytic anemia.
Sources: Literature
Mendeliome v1.4329 ATP11C Lucy Spencer Classified gene: ATP11C as Amber List (moderate evidence)
Mendeliome v1.4329 ATP11C Lucy Spencer Gene: atp11c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4328 ATP11C Lucy Spencer gene: ATP11C was added
gene: ATP11C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP11C was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ATP11C were set to 41523080; 40869043; 37892263; 37671681; 26944472
Phenotypes for gene: ATP11C were set to Hemolytic anemia, congenital, X-linked MIM#301015
Review for gene: ATP11C was set to AMBER
Added comment: PMID: 40869043 reports 3 unrelated families with haemolytic anaemia and ATP11C variants. Probands were all hemizygous boys who had maternally inherited variants, all variants were absent or only has 1 het in gnomad. One family had a frameshift, another ha 2 missense variants in cis, and the third had a -7 splice variant that RT-PCR showed resulted in an in frame insertion. 2 probands were shown to have normal G6PD activity and haemoglobin, the third was not tested. The proband with the ATP11C frameshift also had a de novo missense in ANK1

PMID: 37892263, 37671681, 26944472 report 3 hemizygous male haemolytic anaemia. However 2 of the patients had pathogenic variants in genes associated with spherocytosis SPTA1 and ANK1. The ATP11C variants were absent or rare in gnomad (note papers use different transcripts/p. numbering to gnomad).

PMID: 41523080 reports 2 of the same patients as PMID:40869043 and additionally looked at Val972Met in a very large cohort of blood donors, but this variant is called Val969Met in gnomad where it has thousands of hets and hemizygotes.
Sources: Literature
Mendeliome v1.4327 GPR101 Bryony Thompson Marked gene: GPR101 as ready
Mendeliome v1.4327 GPR101 Bryony Thompson Gene: gpr101 has been classified as Green List (High Evidence).
Mendeliome v1.4327 GPR101 Bryony Thompson changed review comment from: Well-established gene-disease association with a GeneReviews. Heterozygous or hemizygous for a germline variant or somatic duplication.
Sources: Literature; to: Well-established gene-disease association with X-Linked Acrogigantism (has a GeneReviews). Heterozygous or hemizygous for a germline variant or somatic duplication.
Sources: Literature
Mendeliome v1.4327 GPR101 Bryony Thompson Classified gene: GPR101 as Green List (high evidence)
Mendeliome v1.4327 GPR101 Bryony Thompson Gene: gpr101 has been classified as Green List (High Evidence).
Mendeliome v1.4326 GPR101 Bryony Thompson gene: GPR101 was added
gene: GPR101 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR101 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: GPR101 were set to 29389097
Phenotypes for gene: GPR101 were set to pituitary adenoma, growth hormone-secreting, 2 MONDO:0010492
Review for gene: GPR101 was set to GREEN
Added comment: Well-established gene-disease association with a GeneReviews. Heterozygous or hemizygous for a germline variant or somatic duplication.
Sources: Literature
Mendeliome v1.4325 MID2 Bryony Thompson gene: MID2 was added
gene: MID2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MID2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MID2 were set to 24115387
Phenotypes for gene: MID2 were set to non-syndromic X-linked intellectual disability MONDO:0019181
Review for gene: MID2 was set to RED
Added comment: A single family reported
Sources: Literature
Mendeliome v1.4324 HMGB3 Bryony Thompson Marked gene: HMGB3 as ready
Mendeliome v1.4324 HMGB3 Bryony Thompson Gene: hmgb3 has been classified as Red List (Low Evidence).
Mendeliome v1.4324 HMGB3 Bryony Thompson gene: HMGB3 was added
gene: HMGB3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HMGB3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HMGB3 were set to 24993872
Phenotypes for gene: HMGB3 were set to X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome MONDO:0010485
Review for gene: HMGB3 was set to RED
Added comment: A single family reported in 2014, segregating a hemizygous frameshift variant in affected men
Sources: Literature
Mendeliome v1.4323 TTC29 Bryony Thompson Marked gene: TTC29 as ready
Mendeliome v1.4323 TTC29 Bryony Thompson Gene: ttc29 has been classified as Green List (High Evidence).
Mendeliome v1.4323 TTC29 Bryony Thompson Classified gene: TTC29 as Green List (high evidence)
Mendeliome v1.4323 TTC29 Bryony Thompson Gene: ttc29 has been classified as Green List (High Evidence).
Mendeliome v1.4322 TTC29 Bryony Thompson gene: TTC29 was added
gene: TTC29 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC29 were set to 31735292
Phenotypes for gene: TTC29 were set to spermatogenic failure MONDO:0004983
Review for gene: TTC29 was set to GREEN
Added comment: 5 unrelated men with infertility and a supporting null mouse model
Sources: Literature
Mendeliome v1.4321 CCDC146 Bryony Thompson Marked gene: CCDC146 as ready
Mendeliome v1.4321 CCDC146 Bryony Thompson Gene: ccdc146 has been classified as Green List (High Evidence).
Mendeliome v1.4321 CCDC146 Bryony Thompson Classified gene: CCDC146 as Green List (high evidence)
Mendeliome v1.4321 CCDC146 Bryony Thompson Gene: ccdc146 has been classified as Green List (High Evidence).
Mendeliome v1.4320 CCDC146 Bryony Thompson gene: CCDC146 was added
gene: CCDC146 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC146 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC146 were set to 38441556; 39245651
Phenotypes for gene: CCDC146 were set to spermatogenic failure MONDO:0004983
Review for gene: CCDC146 was set to GREEN
Added comment: 3 males with biallelic variants and a supporting infertile mouse model.
Sources: Literature
Mendeliome v1.4319 ARMC12 Bryony Thompson Marked gene: ARMC12 as ready
Mendeliome v1.4319 ARMC12 Bryony Thompson Gene: armc12 has been classified as Green List (High Evidence).
Mendeliome v1.4319 ARMC12 Bryony Thompson Classified gene: ARMC12 as Green List (high evidence)
Mendeliome v1.4319 ARMC12 Bryony Thompson Gene: armc12 has been classified as Green List (High Evidence).
Mendeliome v1.4318 ARMC12 Bryony Thompson gene: ARMC12 was added
gene: ARMC12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARMC12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC12 were set to 35534203; 33536340
Phenotypes for gene: ARMC12 were set to spermatogenic failure MONDO:0004983
Review for gene: ARMC12 was set to GREEN
Added comment: 3 males from 2 families with hom/chet variants and a supporting null mouse model.
Sources: Literature
Mendeliome v1.4317 CFAP61 Bryony Thompson Marked gene: CFAP61 as ready
Mendeliome v1.4317 CFAP61 Bryony Thompson Gene: cfap61 has been classified as Green List (High Evidence).
Mendeliome v1.4317 CFAP61 Bryony Thompson Classified gene: CFAP61 as Green List (high evidence)
Mendeliome v1.4317 CFAP61 Bryony Thompson Gene: cfap61 has been classified as Green List (High Evidence).
Mendeliome v1.4316 CFAP61 Bryony Thompson gene: CFAP61 was added
gene: CFAP61 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP61 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP61 were set to 36659204; 34792097; 35387802; 35174165
Phenotypes for gene: CFAP61 were set to spermatogenic failure MONDO:0004983
Review for gene: CFAP61 was set to GREEN
Added comment: At least 6 unrelated men with chet/hom variants and a supporting mouse model
Sources: Literature
Mendeliome v1.4315 NUP210L Bryony Thompson Marked gene: NUP210L as ready
Mendeliome v1.4315 NUP210L Bryony Thompson Gene: nup210l has been classified as Red List (Low Evidence).
Mendeliome v1.4315 NUP210L Bryony Thompson gene: NUP210L was added
gene: NUP210L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP210L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP210L were set to 20034429; 33332558
Phenotypes for gene: NUP210L were set to spermatogenic failure MONDO:0004983
Review for gene: NUP210L was set to RED
Added comment: Single case from a consanguineous family and a supporting null mouse model.
Sources: Literature
Mendeliome v1.4314 PTPN2 Bryony Thompson Publications for gene: PTPN2 were set to 32499645; 27658548; 39028869
Mendeliome v1.4313 PTPN2 Bryony Thompson edited their review of gene: PTPN2: Added comment: 2 consanguineous cases with homozygous missense variants in PTPN2 (heterozygous individuals unaffected). Phenotypes differ between common variable immunodeficiency with bronchiectasis, or early‑onset Crohn disease with growth failure and neurodevelopmental delay.; Changed rating: RED; Changed publications: 37537852, 35389161; Changed phenotypes: Inborn error of immunity, MONDO:0003778, Syndromic disease, MONDO:0002254; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4313 Bryony Thompson Copied STR RAPGEF2_FAME7_TTTCA from panel Genetic Epilepsy
Mendeliome v1.4313 RAPGEF2_FAME7_TTTCA Bryony Thompson STR: RAPGEF2_FAME7_TTTCA was added
STR: RAPGEF2_FAME7_TTTCA was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for STR: RAPGEF2_FAME7_TTTCA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: RAPGEF2_FAME7_TTTCA were set to 29507423; 30351492; 33791773
Phenotypes for STR: RAPGEF2_FAME7_TTTCA were set to Epilepsy, familial adult myoclonic, 7 MIM#618075
Mendeliome v1.4312 RAPGEF2 Bryony Thompson Marked gene: RAPGEF2 as ready
Mendeliome v1.4312 RAPGEF2 Bryony Thompson Gene: rapgef2 has been classified as Green List (High Evidence).
Mendeliome v1.4312 RAPGEF2 Bryony Thompson Phenotypes for gene: RAPGEF2 were changed from ?Epilepsy, familial adult myoclonic, 7 MIM# 618075 to Neurodevelopmental disorder, MONDO:0700092; amyotrophic lateral sclerosis MONDO:0004976
Mendeliome v1.4311 RAPGEF2 Bryony Thompson Publications for gene: RAPGEF2 were set to 37021642; 30351492; 29507423
Mendeliome v1.4310 RAPGEF2 Bryony Thompson Classified gene: RAPGEF2 as Green List (high evidence)
Mendeliome v1.4310 RAPGEF2 Bryony Thompson Gene: rapgef2 has been classified as Green List (High Evidence).
Mendeliome v1.4309 RAPGEF2 Bryony Thompson reviewed gene: RAPGEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41556274, 30636905; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, amyotrophic lateral sclerosis MONDO:0004976; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4309 EBF2 Zornitza Stark Mode of inheritance for gene: EBF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4308 EBF2 Zornitza Stark edited their review of gene: EBF2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4308 EBF2 Zornitza Stark Classified gene: EBF2 as Amber List (moderate evidence)
Mendeliome v1.4308 EBF2 Zornitza Stark Gene: ebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4307 EBF2 Zornitza Stark edited their review of gene: EBF2: Changed rating: AMBER
Mendeliome v1.4307 EBF2 Zornitza Stark Marked gene: EBF2 as ready
Mendeliome v1.4307 EBF2 Zornitza Stark Gene: ebf2 has been classified as Red List (Low Evidence).
Mendeliome v1.4307 EBF2 Zornitza Stark gene: EBF2 was added
gene: EBF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EBF2 were set to 41615236; 38978649; 29704291
Phenotypes for gene: EBF2 were set to Lipodystrophy, MONDO:0006573, EBF2-related
Review for gene: EBF2 was set to RED
Added comment: PMIDs 38978649 and 41615236 each describe a single patient with a heterozygous nonsense p.Glu165Ter variant and childhood‑onset partial lipodystrophy, providing extensive functional validation. Heterozygous knock‑in mice (Ebf2^E165X/+) recapitulate restricted adipogenesis, extracellular matrix fibrosis, reduced leptin and adiponectin, metabolic impairment on high‑fat diet and mitochondrial gene down‑regulation, supporting pathogenicity. Dominant negative mechanism suggested.

Also note PMID 29704291 reports six affected individuals from one family with a heterozygous missense p.Ala72Val variant and isolated imperforate anus. No functional data provided.
Sources: Literature
Mendeliome v1.4306 FAM111A Zornitza Stark Phenotypes for gene: FAM111A were changed from autosomal dominant Kenny-Caffey syndrome MONDO:0007478 to Kenny-Caffey syndrome, type 2, MIM# 127000
Mendeliome v1.4305 FAM111A Zornitza Stark Publications for gene: FAM111A were set to 23684011; 32996714; 32765931; 33010201
Mendeliome v1.4304 FAM111A Zornitza Stark Mode of inheritance for gene: FAM111A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4303 FAM111A Zornitza Stark reviewed gene: FAM111A: Rating: AMBER; Mode of pathogenicity: None; Publications: 39932783, 39501122; Phenotypes: Kenny-Caffey syndrome, type 2, MIM# 127000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4303 STEAP3 Zornitza Stark Publications for gene: STEAP3 were set to 22031863; 25515317; 26675350
Mendeliome v1.4302 STEAP3 Zornitza Stark Mode of inheritance for gene: STEAP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4301 STEAP3 Zornitza Stark edited their review of gene: STEAP3: Added comment: PMID 38360212 reports two unrelated families with compound heterozygous STEAP3 missense variants (p.I177M, p.T495M) causing childhood-onset microcytic anaemia; functional ferrireductase assays in HeLa cells demonstrate loss of activity. Part of large cohort study, low level of individual detail.; Changed publications: 22031863, 25515317, 26675350, 38360212; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4301 TRU-TCA1-1 Katrina Bell All sources for gene: TRU-TCA1-1 were removed
Mendeliome v1.4300 PTBP1 Zornitza Stark Phenotypes for gene: PTBP1 were changed from Neurodevelopmental disorder (MONDO:0700092), PTBP1-related to STAD syndrome, MIM# 621495
Mendeliome v1.4299 PTBP1 Zornitza Stark reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: STAD syndrome, MIM# 621495; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4299 ATP5B Zornitza Stark Phenotypes for gene: ATP5B were changed from Inherited dystonia, MONDO:0044807, ATP5B-related; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085 to Dystonia 38, susceptibility to, MIM# 621502; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Mendeliome v1.4298 ATP5B Zornitza Stark edited their review of gene: ATP5B: Changed phenotypes: Dystonia 38, susceptibility to, MIM# 621502, Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Mendeliome v1.4298 GDF3 Zornitza Stark Phenotypes for gene: GDF3 were changed from Microphthalmia with coloboma 6, MIM# 613703; Microphthalmia, isolated 7, MIM# 613704 to Microphthalmia with coloboma 6, MIM# 613703; Microphthalmia, isolated 7, MIM# 613704; Klippel-Feil anomaly with laryngeal malformation - 613702
Mendeliome v1.4297 GDF3 Zornitza Stark edited their review of gene: GDF3: Added comment: Single family reported with the skeletal phenotype in 2010, none since. Note they also had ocular abnormalities so unclear if this is a distinct association.; Changed phenotypes: Microphthalmia with coloboma 6 613703, Microphthalmia, isolated 7 613704, Klippel-Feil anomaly with laryngeal malformation - 613702
Mendeliome v1.4297 GDF3 Zornitza Stark Mode of inheritance for gene: GDF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4296 GDF3 Zornitza Stark edited their review of gene: GDF3: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4296 ZFHX3 Zornitza Stark Phenotypes for gene: ZFHX3 were changed from Neurodevelopmental disorder, MONDO:0700092, ZFHX3-related; developmental and epileptic encephalopathy MONDO:0100062, ZFHX3-related to Neurodevelopmental disorder, MONDO:0700092, ZFHX3-related; {Epilepsy, idiopathic generalized, susceptibility to}, MIM#621500
Mendeliome v1.4295 ZFHX3 Zornitza Stark edited their review of gene: ZFHX3: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, ZFHX3-related, {Epilepsy, idiopathic generalized, susceptibility to}, MIM#621500
Mendeliome v1.4295 PTPRF Bryony Thompson gene: PTPRF was added
gene: PTPRF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPRF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPRF were set to 24781087
Phenotypes for gene: PTPRF were set to breasts and/or nipples, aplasia or hypoplasia of, 2 MONDO:0014450
Review for gene: PTPRF was set to RED
Added comment: A single consanguineous family with a homozygous variant
Sources: Literature
Mendeliome v1.4294 Bryony Thompson Copied gene MYL4 from panel Atrial Fibrillation
Mendeliome v1.4294 MYL4 Bryony Thompson gene: MYL4 was added
gene: MYL4 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: MYL4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYL4 were set to 27742809; 27066836; 29080865
Phenotypes for gene: MYL4 were set to atrial fibrillation, familial, 18 MONDO:0015001
Mendeliome v1.4293 CTSO Rylee Peters gene: CTSO was added
gene: CTSO was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CTSO was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTSO were set to 41508845
Phenotypes for gene: CTSO were set to Brain aneurysm, MONDO:0005291, CTSO-related
Review for gene: CTSO was set to RED
Added comment: PMID:41508845 reports 9 individuals from 2 unrelated families with heterozygous missense CTSO variants presenting with familial intracranial aneurysm; an additional 8 relatives were heterozygous for a CTSO variant but had no intracranial aneurysm; 16 unaffected relatives did not have a CTSO variant. The two missense variants identified in these families are present in gnomAD v4, p.(Val316Ile) with 84 hets, p.(Ala43Val) with 683 hets, 1 hom.

In‑vitro VSMC knock‑down and mutant‑expression assays showed reduced CTSO secretion, increased fibronectin deposition, increased cell stiffness; but a causal relationship between CTSO variants and intracranial aneurysm has not been demonstrated in an in‑vivo model
Sources: Literature
Mendeliome v1.4292 CELSR1 Rylee Peters changed review comment from: GREEN rating for monoallelic lymphatic malformation 9, MIM# 619319

GREEN rating for biallelic neurodevelopmental disorder association:
PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants association with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.
PMID: 36453712 describe 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.; to: GREEN rating for monoallelic lymphatic malformation 9, MIM# 619319

GREEN rating for biallelic neurodevelopmental disorder association:
PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants associated with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.
PMID: 36453712 describe 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Mendeliome v1.4292 CELSR1 Rylee Peters Phenotypes for gene: CELSR1 were changed from Lymphatic malformation 9, MIM# 619319 to Lymphatic malformation 9 (MIM#619319); Neurodevelopmental disorder, MONDO:0700092, CELSR1-related
Mendeliome v1.4291 CELSR1 Rylee Peters Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770
Mendeliome v1.4290 CELSR1 Rylee Peters Mode of inheritance for gene: CELSR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4289 CELSR1 Rylee Peters reviewed gene: CELSR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26855770, 31215153, 31403174, 36453712, 38272662, 41530147; Phenotypes: Lymphatic malformation 9 (MIM#619319), Neurodevelopmental disorder, MONDO:0700092, CELSR1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4289 GPD2 Bryony Thompson Marked gene: GPD2 as ready
Mendeliome v1.4289 GPD2 Bryony Thompson Gene: gpd2 has been classified as Red List (Low Evidence).
Mendeliome v1.4289 GPD2 Bryony Thompson gene: GPD2 was added
gene: GPD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPD2 were set to 9070847; 12093800
Phenotypes for gene: GPD2 were set to type 2 diabetes mellitus MONDO:0005148
Review for gene: GPD2 was set to RED
Added comment: Single case with abnormally low activity of mitochondrial GDH and a rare missense variant. Knockout mouse model has features of both glycerol kinase deficiency and hereditary fructose intolerance.
Sources: Literature
Mendeliome v1.4288 GAL Bryony Thompson gene: GAL was added
gene: GAL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GAL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GAL were set to 25691535
Phenotypes for gene: GAL were set to familial temporal lobe epilepsy 8 MONDO:0014650
Review for gene: GAL was set to RED
Added comment: 2 monozygotic male twins with familial temporal lobe epilepsy with a de novo heterozygous missense variant (p.A39E). In vitro functional assay showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2.
Sources: Literature
Mendeliome v1.4287 RUNDC1 Zornitza Stark Marked gene: RUNDC1 as ready
Mendeliome v1.4287 RUNDC1 Zornitza Stark Gene: rundc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4287 RUNDC1 Zornitza Stark Classified gene: RUNDC1 as Amber List (moderate evidence)
Mendeliome v1.4287 RUNDC1 Zornitza Stark Gene: rundc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4286 RUNDC1 Zornitza Stark reviewed gene: RUNDC1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4286 TTBK1 Zornitza Stark Marked gene: TTBK1 as ready
Mendeliome v1.4286 TTBK1 Zornitza Stark Gene: ttbk1 has been classified as Red List (Low Evidence).
Mendeliome v1.4286 TTBK1 Zornitza Stark gene: TTBK1 was added
gene: TTBK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTBK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTBK1 were set to 41545183
Phenotypes for gene: TTBK1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: TTBK1 was set to RED
Added comment: PMID 41545183 reports 2 individuals from a single family with biallelic loss-of-function frameshift variant (p.Thr634ArgfsTer39) presenting with a severe syndromic neurodevelopmental disorder characterized by global developmental delay, microcephaly, progressive spasticity, non‑ambulatory status, and seizures in the older sibling. No functional studies were performed.
Sources: Literature
Mendeliome v1.4285 Zornitza Stark Copied gene C12orf40 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.4285 C12orf40 Zornitza Stark gene: C12orf40 was added
gene: C12orf40 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: C12orf40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C12orf40 were set to 41580510; 37612290; 37604834
Phenotypes for gene: C12orf40 were set to Infertility disorder, MONDO:0005047, C12orf40-related
Mendeliome v1.4284 DHRS3 Zornitza Stark Phenotypes for gene: DHRS3 were changed from Syndromic disease, MONDO:0002254, DHRS3-related to Craniosynostosis-scoliosis syndrome, MIM# 621499
Mendeliome v1.4283 DHRS3 Zornitza Stark edited their review of gene: DHRS3: Changed phenotypes: Craniosynostosis-scoliosis syndrome, MIM# 621499
Mendeliome v1.4283 TMEM189 Chirag Patel Marked gene: TMEM189 as ready
Mendeliome v1.4283 TMEM189 Chirag Patel Gene: tmem189 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4283 TMEM189 Chirag Patel Classified gene: TMEM189 as Amber List (moderate evidence)
Mendeliome v1.4283 TMEM189 Chirag Patel Gene: tmem189 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4282 TMEM189 Chirag Patel gene: TMEM189 was added
gene: TMEM189 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM189 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM189 were set to 41491239
Phenotypes for gene: TMEM189 were set to Neurodevelopmental disorder, MONDO:0700092, PEDS1-related
Review for gene: TMEM189 was set to AMBER
Added comment: 2 individuals from 2 unrelated consanguineous families presenting with microcephaly, global developmental delay, growth retardation, dysmorphic facial features and congenital cataracts (in one case). Both individuals had the same rare homozygous frameshift variant (c.104delC, p.Ala35Valfs*16) in PEDS1 gene (aka TMEM189). The variant segregated in the family. PEDS1 encodes the plasmanylethanolamine desaturase that catalyzes the final step of plasmalogen biosynthesis. Functional studies show the mutant protein is unstable and undetectable in COS7 cells, and mouse Peds1‑/‑ knockouts display microcephaly and neuroanatomical defects mirroring the human phenotype. Rescue of neuronal migration deficits by RNAi‑resistant wild‑type PEDS1 confirms loss‑of‑function as the disease mechanism.
Sources: Literature
Mendeliome v1.4281 LRPAP1 Bryony Thompson Marked gene: LRPAP1 as ready
Mendeliome v1.4281 LRPAP1 Bryony Thompson Gene: lrpap1 has been classified as Green List (High Evidence).
Mendeliome v1.4281 LRPAP1 Bryony Thompson Classified gene: LRPAP1 as Green List (high evidence)
Mendeliome v1.4281 LRPAP1 Bryony Thompson Gene: lrpap1 has been classified as Green List (High Evidence).
Mendeliome v1.4280 LRPAP1 Bryony Thompson gene: LRPAP1 was added
gene: LRPAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRPAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRPAP1 were set to 23830514; 25525168; 36261846; 39444998
Phenotypes for gene: LRPAP1 were set to myopia 23, autosomal recessive MONDO:0014183
Review for gene: LRPAP1 was set to GREEN
Added comment: At least 4 families reported with homozygous variants, and a supporting zebrafish model
Sources: Literature
Mendeliome v1.4279 ACR Bryony Thompson Marked gene: ACR as ready
Mendeliome v1.4279 ACR Bryony Thompson Gene: acr has been classified as Red List (Low Evidence).
Mendeliome v1.4279 ACR Bryony Thompson gene: ACR was added
gene: ACR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACR were set to 37004249
Phenotypes for gene: ACR were set to spermatogenic failure MONDO:0004983
Review for gene: ACR was set to RED
Added comment: A single consanguineous family reported with a homozygous stopgain variant (c.167G>A, p.Trp56*) and supporting in vitro assay.
Sources: Literature
Mendeliome v1.4278 FGF10 Bryony Thompson Deleted their comment
Mendeliome v1.4278 FGF10 Bryony Thompson edited their review of gene: FGF10: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4278 SLC7A8 Zornitza Stark Marked gene: SLC7A8 as ready
Mendeliome v1.4278 SLC7A8 Zornitza Stark Gene: slc7a8 has been classified as Red List (Low Evidence).
Mendeliome v1.4278 Zornitza Stark Copied gene SLC7A8 from panel Cataract
Mendeliome v1.4278 SLC7A8 Zornitza Stark gene: SLC7A8 was added
gene: SLC7A8 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SLC7A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A8 were set to 40229141; 31231240
Phenotypes for gene: SLC7A8 were set to Cataract, MONDO:0005129, SLC7A8-related
Mendeliome v1.4277 RRAGA Zornitza Stark Marked gene: RRAGA as ready
Mendeliome v1.4277 RRAGA Zornitza Stark Gene: rraga has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4277 Zornitza Stark Copied gene RRAGA from panel Cataract
Mendeliome v1.4277 RRAGA Zornitza Stark gene: RRAGA was added
gene: RRAGA was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RRAGA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RRAGA were set to 27294265
Phenotypes for gene: RRAGA were set to Cataract, MONDO:0005129, RRAGA-related
Mendeliome v1.4276 PRX Zornitza Stark Phenotypes for gene: PRX were changed from Charcot-Marie-Tooth disease type 4 MONDO:0018995 to Charcot-Marie-Tooth disease type 4 MONDO:0018995; Cataract, MONDO:0005129, PRX-related
Mendeliome v1.4275 PRX Zornitza Stark Publications for gene: PRX were set to 11133365; 11157804; 15197604; 21079185; 22847150; 10839370; 32460404; 31523542; 31426691
Mendeliome v1.4274 PRX Zornitza Stark edited their review of gene: PRX: Added comment: PMIDs 27081207 (3 patients, 1 family), 36161833 (1 patient, 1 family) and 41230902 (7 patients, 4 families) report heterozygous PRX missense and splice‑site variants segregating with autosomal dominant congenital cataract. This association appears distinct from the association with CMT. PMID 41230902 specifically has splice‑region variants in the final intron of PRXb, and suggests GoF or dominant negative mechanism.; Changed publications: 11133365, 11157804, 15197604, 21079185, 22847150, 10839370, 32460404, 31523542, 31426691, 27081207, 36161833, 41230902; Changed phenotypes: Charcot-Marie-Tooth disease, type 4F, MIM# 614895, Dejerine-Sottas disease, MIM# 145900, Cataract, MONDO:0005129, PRX-related
Mendeliome v1.4274 RUNDC1 Lilian Downie gene: RUNDC1 was added
gene: RUNDC1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: RUNDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RUNDC1 were set to Neurodevelopmental disorder with pituitary anomalies
Review for gene: RUNDC1 was set to AMBER
Added comment: Unpublished, cohort from GeneMatcher with biallelic variants in infants with panhypopit and dev delay.
Dr. Adam Jackson and Dr. Siddharth Banka (Manchester putting cohort together)
Sources: Other
Mendeliome v1.4273 SCAMP5 Lucy Spencer Phenotypes for gene: SCAMP5 were changed from Neurodevelopmental disorder, MONDO:0700092, SCAMP5-related to Neurodevelopmental disorder, MONDO:0700092, SCAMP5-related; Epilepsy (MONDO:0005027), SCAMP5-related
Mendeliome v1.4272 SCAMP5 Lucy Spencer Publications for gene: SCAMP5 were set to 31439720; 33390987
Mendeliome v1.4271 SCAMP5 Lucy Spencer Mode of inheritance for gene: SCAMP5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4270 SCAMP5 Lucy Spencer reviewed gene: SCAMP5: Rating: AMBER; Mode of pathogenicity: None; Publications: 32020363; Phenotypes: Epilepsy (MONDO:0005027), SCAMP5-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4270 FGF10 Bryony Thompson edited their review of gene: FGF10: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4270 FGF10 Bryony Thompson changed review comment from: 2 families with a lethal congenital alveolar dysplasia phenotype with compound heterozygous coding‑loss‑of‑function with non-coding SNVs in a predicted lung-specific enhancer region.; to: Amber for biallelic - 2 families with a lethal congenital alveolar dysplasia phenotype with compound heterozygous coding‑loss‑of‑function with non-coding SNVs in a predicted lung-specific enhancer region.
Mendeliome v1.4270 FGF10 Bryony Thompson edited their review of gene: FGF10: Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4270 FGF10 Bryony Thompson edited their review of gene: FGF10: Added comment: 2 families with a lethal congenital alveolar dysplasia phenotype with compound heterozygous coding‑loss‑of‑function with non-coding SNVs in a predicted lung-specific enhancer region.; Changed rating: AMBER; Changed publications: 30639323; Changed phenotypes: Familial primary pulmonary hypoplasia, MONDO:0009936; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4270 Bryony Thompson Copied gene RPL23 from panel Haematological malignancies
Mendeliome v1.4270 RPL23 Bryony Thompson gene: RPL23 was added
gene: RPL23 was added to Mendeliome. Sources: Expert Review Red,Curated sources
Mode of inheritance for gene: RPL23 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL23 were set to 28297620
Phenotypes for gene: RPL23 were set to Osteosarcoma, soft tissue sarcomas; Diamond Blackfan Anemia; MDS, AML; Class: BM failure syndrome (typ AR)
Mendeliome v1.4269 LAMP3 Zornitza Stark Publications for gene: LAMP3 were set to 40023045; 34161347
Mendeliome v1.4268 LAMP3 Zornitza Stark Classified gene: LAMP3 as Green List (high evidence)
Mendeliome v1.4268 LAMP3 Zornitza Stark Gene: lamp3 has been classified as Green List (High Evidence).
Mendeliome v1.4267 LAMP3 Zornitza Stark edited their review of gene: LAMP3: Added comment: PMID 41653023 reports 13 individuals with biallelic variants in LAMP3, presenting with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood. All symptomatic participants had ground glass opacities early in life and lung fibrosis later in life.; Changed rating: GREEN; Changed publications: 40023045, 34161347, 41653023
Mendeliome v1.4267 CPT1C Zornitza Stark Tag disputed tag was added to gene: CPT1C.
Mendeliome v1.4267 CPT1C Zornitza Stark Publications for gene: CPT1C were set to 25751282; 23973755; 30564185
Mendeliome v1.4266 CPT1C Zornitza Stark Classified gene: CPT1C as Amber List (moderate evidence)
Mendeliome v1.4266 CPT1C Zornitza Stark Gene: cpt1c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4265 CPT1C Zornitza Stark edited their review of gene: CPT1C: Added comment: Disputed in PMID 41312619: among >170 CPT1C LOF carriers in the UKBB (n = 150,119), none exhibited HSP phenotypes. Among 585 HSP patients from Can-HSP, there were no patients with CPT1C LOF variants. In the GENESIS cohort (n = 21,217), three individuals carrying CPT1C LOF variants were also diagnosed with HSP; however, all three also carried pathogenic variants in established HSP-associated genes.; Changed rating: AMBER; Changed publications: 30564185, 41312619
Mendeliome v1.4265 Bryony Thompson Copied gene CDC5L from panel Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic
Mendeliome v1.4265 CDC5L Bryony Thompson gene: CDC5L was added
gene: CDC5L was added to Mendeliome. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: CDC5L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC5L were set to 24429398
Phenotypes for gene: CDC5L were set to Congenital abnormalities of the kidneys and urinary tract
Mendeliome v1.4264 RBM7 Bryony Thompson edited their review of gene: RBM7: Changed rating: RED
Mendeliome v1.4264 RBM7 Bryony Thompson Classified gene: RBM7 as Red List (low evidence)
Mendeliome v1.4264 RBM7 Bryony Thompson Gene: rbm7 has been classified as Red List (Low Evidence).
Mendeliome v1.4263 PMP2 Bryony Thompson Classified gene: PMP2 as Green List (high evidence)
Mendeliome v1.4263 PMP2 Bryony Thompson Gene: pmp2 has been classified as Green List (High Evidence).
Mendeliome v1.4262 MAP2K4 Sangavi Sivagnanasundram Classified gene: MAP2K4 as Green List (high evidence)
Mendeliome v1.4262 MAP2K4 Sangavi Sivagnanasundram Gene: map2k4 has been classified as Green List (High Evidence).
Mendeliome v1.4261 MAP2K4 Sangavi Sivagnanasundram gene: MAP2K4 was added
gene: MAP2K4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAP2K4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAP2K4 were set to 41480045
Phenotypes for gene: MAP2K4 were set to Neurodevelopmental disorder, MONDO:0700092
Mode of pathogenicity for gene: MAP2K4 was set to Other
Review for gene: MAP2K4 was set to GREEN
Added comment: PMID 41480045 reports ten individuals from ten unrelated families with heterozygous de novo loss-of-function or missense MAP2K4 variants presenting with a syndromic neurodevelopmental disorder characterized by developmental delay/intellectual disability, epilepsy, and genitourinary and musculoskeletal congenital anomalies. All the reported variants were absent in gnomAD v4.1.

DD, ID - present in the majority of the reported individuals
CAKUT-like phenotypes reported in 5 individuals
Reports of hypotonia in three individuals
Epilepsy was reported in 4 individuals

A functional study using CRISPR-edited iPSC-derived neurons demonstrates reduced MP2K4 protein and impaired JNK signalling however, more evidence is required to confirm loss of function as the mechanism of disease. There are no pathogenic variants reported in ClinVar in this gene in the germline context.
Sources: Literature
Mendeliome v1.4260 VPS18 Bryony Thompson Marked gene: VPS18 as ready
Mendeliome v1.4260 VPS18 Bryony Thompson Gene: vps18 has been classified as Red List (Low Evidence).
Mendeliome v1.4260 VPS18 Bryony Thompson gene: VPS18 was added
gene: VPS18 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VPS18 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: VPS18 were set to 41526335
Phenotypes for gene: VPS18 were set to Inborn error of immunity, MONDO:0003778
Review for gene: VPS18 was set to RED
Added comment: PMID 41526335 reports a single individual from one unrelated family with a heterozygous loss‑of‑function stop‑gain VPS18 variant (c.700C>T, p.Arg234Ter) presenting with congenital neutropenia, maturation arrest of neutrophils and recurrent infections. Human iPSC knock‑in, zebrafish and mouse models recapitulate the neutrophil deficiency, supporting a haploinsufficiency mechanism with dominant inheritance and incomplete penetrance.
Sources: Literature
Mendeliome v1.4259 CTNND2 Zornitza Stark Classified gene: CTNND2 as Green List (high evidence)
Mendeliome v1.4259 CTNND2 Zornitza Stark Gene: ctnnd2 has been classified as Green List (High Evidence).
Mendeliome v1.4258 CTNND2 Zornitza Stark edited their review of gene: CTNND2: Added comment: PMID 41502569 (preprint) reports phenotypic and molecular information for 57 individuals, 42 previously unpublished, with heterozygous CTNND2 variants. The 41 CTNND2 variants included 12 previously reported loss-of-function- and one missense variant, and 28 novel variants comprising 10 missense and 18 predicted loss-of-function changes. Eight of the novel variants occurred de novo, and 12 were inherited from a parent with a neurodevelopmental phenotype. The most common clinical features were developmental delay (90%), intellectual disability (74%), and behavioral abnormalities (79%). Functional studies revealed impaired early neurogenesis in one patient-derived line, characterized by aberrant neural rosette formation. Transcriptome analysis showed dysregulated WNT signaling, and partial rescue of these defects was achieved by modulating the WNT pathway, highlighting δ-catenin's role in early neural development.

Note several of the reported missense variants in this gene have high gnomAD counts so these should be interpreted with caution. Nevertheless, large number of individuals reported now with LoF variants and NDD phenotype.; Changed rating: GREEN; Changed publications: 25839933, 29127138, 25807484, 41502569; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CTNND2-related
Mendeliome v1.4258 GDF6 Lucy Spencer Phenotypes for gene: GDF6 were changed from Klippel-Feil syndrome 1, autosomal dominant 118100; Leber congenital amaurosis 17 615360; Microphthalmia with coloboma 6, digenic 613703; Microphthalmia, isolated 4 613094; Multiple synostoses syndrome 4 617898; CAKUT to Multiple synostoses syndrome 4 MIM#617898; Klippel-Feil syndrome 1, autosomal dominant MIM#118100; Leber congenital amaurosis 17 MIM615360; Microphthalmia, isolated 4 MIM#613094
Mendeliome v1.4257 GDF6 Lucy Spencer Publications for gene: GDF6 were set to 18425797; 19129173; 32737436
Mendeliome v1.4256 GDF6 Lucy Spencer reviewed gene: GDF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26643732, 29130651, 30733656, 18425797, 34573339, 23307924, 19129173, 20494911, 21070663, 24033328, 25457163; Phenotypes: Multiple synostoses syndrome 4 MIM#617898, Klippel-Feil syndrome 1, autosomal dominant MIM#118100, Leber congenital amaurosis 17 MIM615360, Microphthalmia, isolated 4 MIM#613094; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4256 PGBD5 Zornitza Stark Marked gene: PGBD5 as ready
Mendeliome v1.4256 PGBD5 Zornitza Stark Gene: pgbd5 has been classified as Green List (High Evidence).
Mendeliome v1.4256 Zornitza Stark Copied gene PGBD5 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.4256 PGBD5 Zornitza Stark gene: PGBD5 was added
gene: PGBD5 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PGBD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGBD5 were set to 41533792
Phenotypes for gene: PGBD5 were set to Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, MIM# 621482
Mendeliome v1.4255 ALDH6A1 Sangavi Sivagnanasundram changed review comment from: Classified as LIMITED by ClinGen Aminoacidopathy GCEP on 15/01/2026 - https://search.clinicalgenome.org/CCID:004096

ClinGen reports the same 5 probands mentioned below with biochemical abnormalities.
Their reasoning for classifying this GDA as limited is:
"There is the question of whether the additional symptoms of some individuals are related to this disorder, although that is unrelated to the biochemical abnormality and the response to modified diet seems to indicate a connection."

Given the biochemical abnormality, gene remain as GREEN.; to: Classified as LIMITED by ClinGen Aminoacidopathy GCEP on 09/01/2026 - https://search.clinicalgenome.org/CCID:004096

ClinGen reports the same 5 probands mentioned below with biochemical abnormalities.
Their reasoning for classifying this GDA as limited is:
"There is the question of whether the additional symptoms of some individuals are related to this disorder, although that is unrelated to the biochemical abnormality and the response to modified diet seems to indicate a connection."

Given the biochemical abnormality, gene remain as GREEN.
Mendeliome v1.4255 ALDH6A1 Sangavi Sivagnanasundram reviewed gene: ALDH6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004096; Phenotypes: methylmalonate semialdehyde dehydrogenase deficiency MONDO:0013579; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4255 TMEM168 Sangavi Sivagnanasundram commented on gene: TMEM168
Mendeliome v1.4255 TMEM168 Sangavi Sivagnanasundram Classified gene: TMEM168 as No list
Mendeliome v1.4255 TMEM168 Sangavi Sivagnanasundram Gene: tmem168 has been removed from the panel.
Mendeliome v1.4254 TMEM168 Sangavi Sivagnanasundram Deleted their review
Mendeliome v1.4254 TMEM168 Sangavi Sivagnanasundram gene: TMEM168 was added
gene: TMEM168 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: TMEM168 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM168 were set to https://search.clinicalgenome.org/CCID:009114
Phenotypes for gene: TMEM168 were set to Brugada syndrome MONDO:0015263
Review for gene: TMEM168 was set to RED
Added comment: Classified as DISPUTED by ClinGen Hereditary Cardiovascular Disease GCEP on 15/01/2026- https://search.clinicalgenome.org/CCID:009114
Sources: ClinGen
Mendeliome v1.4253 IL21 Sangavi Sivagnanasundram edited their review of gene: IL21: Changed rating: RED
Mendeliome v1.4253 IL21 Sangavi Sivagnanasundram changed review comment from: Classified as LIMITED by CliNGen Primary Immune Regulatory Disorders GCEP on 20/01/2026 - https://search.clinicalgenome.org/CCID:005133

Remain as Amber. ClinGen reports the same proband and siblings as below along with supportive functional assays; to: Classified as LIMITED by CliNGen Primary Immune Regulatory Disorders GCEP on 20/01/2026 - https://search.clinicalgenome.org/CCID:005133

Remain as RED. ClinGen reports the same proband and siblings as below along with supportive functional assays however only one reported proband with biallelic variant in this gene.
Mendeliome v1.4253 IL21 Sangavi Sivagnanasundram reviewed gene: IL21: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: IL21-related infantile inflammatory bowel disease MONDO:0014338; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4253 ABCC8 Sangavi Sivagnanasundram reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hyperinsulinism MONDO:0002177, hyperinsulinemic hypoglycemia, familial, 1 MONDO:0009734; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4253 TWNK Sangavi Sivagnanasundram changed review comment from: Classified as DEFINITIVE by ClinGen Hearing Loss VCEP on 21/01/2026 - https://search.clinicalgenome.org/CCID:009173; to: Classified as DEFINITIVE by ClinGen Hearing Loss VCEP on 21/01/2026 - https://search.clinicalgenome.org/CCID:009173

"This condition is characterized by childhood-onset, progressive, and moderate-to-profound hearing loss, as well as ocular anomalies (such as nystagmus and ophthalmoplegia); ataxia; hypotonia; neuropathy; seizures; brain structural anomalies (including cerebellar atrophy); demyelination; and, in females, amenorrhea/gonadal dysgenesis."
Mendeliome v1.4253 GRAP Sangavi Sivagnanasundram edited their review of gene: GRAP: Changed phenotypes: nonsyndromic genetic hearing loss MONDO:0019497
Mendeliome v1.4253 TWNK Sangavi Sivagnanasundram reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:009173; Phenotypes: Perrault syndrome 5 MONDO:0014504; Mode of inheritance: None
Mendeliome v1.4253 GRAP Sangavi Sivagnanasundram reviewed gene: GRAP: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:009156; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.4253 ABCD4 Sangavi Sivagnanasundram reviewed gene: ABCD4: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004015; Phenotypes: methylmalonic acidemia with homocystinuria, type cblJ MONDO:0013925; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4253 LDB3 Sangavi Sivagnanasundram reviewed gene: LDB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: dilated cardiomyopathy MONDO:0005021, hypertrophic cardiomyopathy MONDO:0005045, arrhythmogenic right ventricular cardiomyopathy MONDO:0016587; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4253 POLR1C Sangavi Sivagnanasundram reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:009178; Phenotypes: POLR1C-related disorder MONDO:0700278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4253 CTC1 Sangavi Sivagnanasundram reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:009177; Phenotypes: cerebroretinal microangiopathy with calcifications and cysts 1 MONDO:0024564; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4253 RAP1B Sangavi Sivagnanasundram reviewed gene: RAP1B: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005970; Phenotypes: thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies MONDO:0958000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4253 AKT2 Chirag Patel commented on gene: AKT2
Mendeliome v1.4253 ITCH Chirag Patel Phenotypes for gene: ITCH were changed from Syndromic multisystem autoimmune disease due to ITCH deficiency, MONDO:0013245 to Syndromic multisystem autoimmune disease due to ITCH deficiency, MONDO:0013245
Mendeliome v1.4252 ITCH Chirag Patel Phenotypes for gene: ITCH were changed from Autoimmune disease, multisystem, with facial dysmorphism, MIM#613385 to Syndromic multisystem autoimmune disease due to ITCH deficiency, MONDO:0013245
Mendeliome v1.4251 Chirag Patel Added reviews for gene ITCH from panel Disorders of immune dysregulation
Mendeliome v1.4250 NEUROD1 Chirag Patel changed review comment from: ClinGen DEFINITIVE (Mar 2021)
https://search.clinicalgenome.org/CCID:005622

At least 5 variants (missense and nonsense) have been reported in at least 8 probands in association with a phenotype consisting of neonatal diabetes, intrauterine growth retardation, cerebellar hypoplasia, sensorineural deafness, visual impairment, and intellectual disability. This gene-disease relationship is supported by functional assays, expression studies, and animal models.

Note: ClinGen LIMITED (Oct 2021) for autosomal dominant NEUROD1-related diabetes.; to: ClinGen MODERATE (Mar 2021)
https://search.clinicalgenome.org/CCID:005622

At least 5 variants (missense and nonsense) have been reported in at least 8 probands in association with a phenotype consisting of neonatal diabetes, intrauterine growth retardation, cerebellar hypoplasia, sensorineural deafness, visual impairment, and intellectual disability. This gene-disease relationship is supported by functional assays, expression studies, and animal models.

Note: ClinGen LIMITED (Oct 2021) for autosomal dominant NEUROD1-related diabetes.
Mendeliome v1.4250 NEUROD1 Chirag Patel Phenotypes for gene: NEUROD1 were changed from Maturity-onset diabetes of the young 6, MIM#606394; Retinitis pigmentosa, retinopathy, permanent neonatal diabetes to Monogenic diabetes, MONDO:0015967; Retinitis pigmentosa
Mendeliome v1.4249 NEUROD1 Chirag Patel Publications for gene: NEUROD1 were set to 25477324; 25684977; 22784109; 29521454
Mendeliome v1.4248 Chirag Patel Added reviews for gene NEUROD1 from panel Monogenic Diabetes
Mendeliome v1.4247 CAV1 Chirag Patel Publications for gene: CAV1 were set to 18237401; 25898808; 11739396; 18211975; 27717241; 26176221; 33836561; 33776068; 32502478; 22474227; 28768485
Mendeliome v1.4246 Chirag Patel Added reviews for gene CAV1 from panel Monogenic Diabetes
Mendeliome v1.4245 ADRA2A Chirag Patel Marked gene: ADRA2A as ready
Mendeliome v1.4245 ADRA2A Chirag Patel Gene: adra2a has been classified as Red List (Low Evidence).
Mendeliome v1.4245 NSMCE2 Chirag Patel Phenotypes for gene: NSMCE2 were changed from SECKEL SYNDROME 10 to Seckel syndrome 10, MONDO:0014991
Mendeliome v1.4244 Chirag Patel Copied gene ADRA2A from panel Lipodystrophy_Lipoatrophy
Mendeliome v1.4244 ADRA2A Chirag Patel gene: ADRA2A was added
gene: ADRA2A was added to Mendeliome. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ADRA2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADRA2A were set to 27376152
Phenotypes for gene: ADRA2A were set to Lipodystrophy, familial partial, type 8, OMIM #620679
Mendeliome v1.4243 NSMCE2 Chirag Patel reviewed gene: NSMCE2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Seckel syndrome 10, MONDO:0014991; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4243 LIPE Chirag Patel reviewed gene: LIPE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: LIPE-related familial partial lipodystrophy, MONDO:0014431; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4243 RNU6ATAC Chirag Patel Tag non-coding gene tag was added to gene: RNU6ATAC.
Mendeliome v1.4243 RNU6ATAC Chirag Patel Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes
Mendeliome v1.4242 RNU6ATAC Chirag Patel Classified gene: RNU6ATAC as Amber List (moderate evidence)
Mendeliome v1.4242 RNU6ATAC Chirag Patel Gene: rnu6atac has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4241 RNU6ATAC Chirag Patel reviewed gene: RNU6ATAC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: neonatal diabetes, humoral immunue defect, microcephaly, developmental delay.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4241 STAT1 Chirag Patel Phenotypes for gene: STAT1 were changed from Immunodeficiency 31A, mycobacteriosis, autosomal dominant, MIM# 614892; Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, MIM# 613796; Immunodeficiency 31C, chronic mucocutaneous candidiasis, autosomal dominant, MIM# 614162 to Immunodeficiency 31A, mycobacteriosis, autosomal dominant, MIM# 614892; Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, MIM# 613796; Immunodeficiency 31C, chronic mucocutaneous candidiasis, autosomal dominant, MIM# 614162; Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome MONDO:0013599
Mendeliome v1.4240 Chirag Patel Added reviews for gene STAT1 from panel Monogenic Diabetes
Mendeliome v1.4239 PLIN1 Chirag Patel Tag disputed was removed from gene: PLIN1.
Mendeliome v1.4239 PLIN1 Chirag Patel Phenotypes for gene: PLIN1 were changed from Lipodystrophy, familial partial, type 4, MIM# 613877 to PLIN1-related familial partial lipodystrophy, MONDO:0013478
Mendeliome v1.4238 PLIN1 Chirag Patel Publications for gene: PLIN1 were set to 21345103; 31504636; 30020498; 25114292
Mendeliome v1.4237 PLIN1 Chirag Patel Classified gene: PLIN1 as Green List (high evidence)
Mendeliome v1.4237 PLIN1 Chirag Patel Gene: plin1 has been classified as Green List (High Evidence).
Mendeliome v1.4236 Chirag Patel Added reviews for gene PLIN1 from panel Monogenic Diabetes
Mendeliome v1.4235 ADAM17 Zornitza Stark changed review comment from: Missense variant identified in 7 individuals from a 4-generation family. Supportive mouse model. RED for this MOI.; to: Association with hypotrichosis: missense variant identified in 7 individuals from a 4-generation family. Supportive mouse model. RED for this MOI.
Mendeliome v1.4235 ADAM17 Zornitza Stark changed review comment from: Comment when marking as ready: Association with IBD -- two families and a mouse model.; to: Comment when marking as ready: Association with IBD -- two families and a mouse model. GREEN for this MOI/association.
Mendeliome v1.4235 ADAM17 Zornitza Stark changed review comment from: Comment when marking as ready: Two families and a mouse model.; to: Comment when marking as ready: Association with IBD -- two families and a mouse model.
Mendeliome v1.4235 ADAM17 Zornitza Stark edited their review of gene: ADAM17: Added comment: Missense variant identified in 7 individuals from a 4-generation family. Supportive mouse model. RED for this MOI.; Changed rating: RED; Changed publications: 38771644; Changed phenotypes: Hypotrichosis 16, MIM# 621490; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4235 KDM2B Zornitza Stark reviewed gene: KDM2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalities, MIM# 621474; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4235 COX18 Zornitza Stark Phenotypes for gene: COX18 were changed from Mitochondrial disease (MONDO:0044970), COX18-related to Mitochondrial complex IV deficiency, nuclear type 25, MIM# 621487; Charcot-Marie-Tooth disease, axonal, type 2MM, MIM# 621488
Mendeliome v1.4234 COX18 Zornitza Stark reviewed gene: COX18: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 25, MIM# 621487, Charcot-Marie-Tooth disease, axonal, type 2MM, MIM# 621488; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4234 FOXH1 Chirag Patel Phenotypes for gene: FOXH1 were changed from Congenital heart disease to Congenital heart disease
Mendeliome v1.4234 FOXH1 Chirag Patel Phenotypes for gene: FOXH1 were changed from Congenital heart disease to Congenital heart disease
Mendeliome v1.4233 FOXH1 Chirag Patel Phenotypes for gene: FOXH1 were changed from Congenital heart disease; holoprosencephaly to Congenital heart disease
Mendeliome v1.4232 SMARCA1 Zornitza Stark Publications for gene: SMARCA1 were set to 26740508; 26539891; 29249292; 37841849
Mendeliome v1.4231 SMARCA1 Zornitza Stark edited their review of gene: SMARCA1: Added comment: Now published.; Changed publications: 37841849, 41213919
Mendeliome v1.4231 Chirag Patel Added reviews for gene KDM1A from panel Primary nodular adrenocortical disease
Mendeliome v1.4230 MYADML2 Zornitza Stark Phenotypes for gene: MYADML2 were changed from Cranial asymmetry, reduced bone maturation, multiple dislocations, lumbar lordosis, and prominent clavicles to MYADML2-related connective tissue disroder MONDO:0003900
Mendeliome v1.4229 GDF5 Zornitza Stark Phenotypes for gene: GDF5 were changed from Brachydactyly MONDO:0021004, GDF5-related; Acromelic dysplasia MONDO:0019695, GDF5-related; Type A1C brachydactyly (MIM#615072); Type A2 brachydactyly, (MIM#112600); Type C brachydactyly (MIM#113100); Grebe type chondrodysplasia (MIM#200700); Du Pan syndrome (MIM#228900); Multiple synostoses syndrome 2 (MIM#610017); Proximal Symphalangism 1B (MIM#615298) to Brachydactyly MONDO:0021004, GDF5-related; Acromelic dysplasia MONDO:0019695, GDF5-related; Grebe type chondrodysplasia (MIM#200700); Du Pan syndrome (MIM#228900); Multiple synostoses syndrome 2 (MIM#610017); Proximal Symphalangism 1B (MIM#615298)
Mendeliome v1.4228 OXA1L Zornitza Stark Phenotypes for gene: OXA1L were changed from Encephalopathy; hypotonia; developmental delay to OXA1L-related combined oxidative phosphorylation deficiency MONDO:0000732
Mendeliome v1.4227 PAICS Zornitza Stark Phenotypes for gene: PAICS were changed from Polyhydramnios; multiple congenital abnormalities to PAICS deficiency MONDO:0859003
Mendeliome v1.4226 PAX3 Zornitza Stark Publications for gene: PAX3 were set to 20301703; 30854529
Mendeliome v1.4225 PAX3 Zornitza Stark Mode of inheritance for gene: PAX3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4224 DARS2 Zornitza Stark Phenotypes for gene: DARS2 were changed from Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105 to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105; Charcot-Marie-Tooth disease, axonal, type 2LL, MIM# 621485
Mendeliome v1.4223 DARS2 Zornitza Stark Publications for gene: DARS2 were set to 17384640; 15002045; 16788019
Mendeliome v1.4222 DARS2 Zornitza Stark edited their review of gene: DARS2: Added comment: PMID 40814755 reports 5 individuals from 3 unrelated families with CMT.; Changed publications: 17384640, 15002045, 16788019, 40814755; Changed phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105, Charcot-Marie-Tooth disease, axonal, type 2LL, MIM# 621485
Mendeliome v1.4222 SPART Zornitza Stark Marked gene: SPART as ready
Mendeliome v1.4222 SPART Zornitza Stark Gene: spart has been classified as Green List (High Evidence).
Mendeliome v1.4222 Zornitza Stark Copied gene SPART from panel Hereditary Spastic Paraplegia
Mendeliome v1.4222 SPART Zornitza Stark gene: SPART was added
gene: SPART was added to Mendeliome. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: SPART was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPART were set to 12134148; 20437587; 26003402; 27112432; 31535723; 31535723; 28875386; 28679690
Phenotypes for gene: SPART were set to Troyer syndrome, MIM# 275900; SPG20; MONDO:0010156
Mendeliome v1.4221 SCN1B Zornitza Stark reviewed gene: SCN1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4221 SCN1B Zornitza Stark Marked gene: SCN1B as ready
Mendeliome v1.4221 SCN1B Zornitza Stark Gene: scn1b has been classified as Green List (High Evidence).
Mendeliome v1.4221 Zornitza Stark Copied gene SCN1B from panel Genetic Epilepsy
Mendeliome v1.4221 SCN1B Zornitza Stark gene: SCN1B was added
gene: SCN1B was added to Mendeliome. Sources: Expert Review Green,Victorian Clinical Genetics Services,Australian Genomics Health Alliance Epilepsy Flagship
Mode of inheritance for gene: SCN1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SCN1B were set to 19710327; 28218389; 23148524
Phenotypes for gene: SCN1B were set to Developmental and epileptic encephalopathy (MONDO:0100062); generalized epilepsy with febrile seizures plus (MONDO:0018214)
Mendeliome v1.4220 GGCX Zornitza Stark Phenotypes for gene: GGCX were changed from Vitamin K-dependent clotting factors, combined deficiency of, 1, MIM# 277450 to Vitamin K-dependent clotting factors, combined deficiency of, 1, MIM# 277450; pulmonary arterial hypertension MONDO:0015924
Mendeliome v1.4219 GGCX Zornitza Stark Publications for gene: GGCX were set to 32785662; 30531603; 26758921
Mendeliome v1.4218 GGCX Zornitza Stark Mode of inheritance for gene: GGCX was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4217 Zornitza Stark Added reviews for gene GGCX from panel Pulmonary Arterial Hypertension
Mendeliome v1.4216 ARHGAP19 Zornitza Stark Phenotypes for gene: ARHGAP19 were changed from Motor Peripheral Neuropathy; MONDO:0002316; ARHGAP19 related to Charcot-Marie-Tooth disease, axonal, type 2KK, MIM# 621466
Mendeliome v1.4215 ARHGAP19 Zornitza Stark reviewed gene: ARHGAP19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2KK, MIM# 621466; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4215 APPL1 Zornitza Stark Publications for gene: APPL1 were set to 26073777; 36208030
Mendeliome v1.4214 APPL1 Zornitza Stark reviewed gene: APPL1: Rating: RED; Mode of pathogenicity: None; Publications: 40779032; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.4214 Chirag Patel Added reviews for gene AIRE from panel Disorders of immune dysregulation
Mendeliome v1.4213 GINS4 Zornitza Stark Publications for gene: GINS4 were set to 36345943
Mendeliome v1.4212 GINS4 Zornitza Stark Classified gene: GINS4 as Amber List (moderate evidence)
Mendeliome v1.4212 GINS4 Zornitza Stark Gene: gins4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4211 GINS4 Zornitza Stark reviewed gene: GINS4: Rating: AMBER; Mode of pathogenicity: None; Publications: 39914554, 40510848; Phenotypes: combined immunodeficiency MONDO:0015131; Mode of inheritance: None
Mendeliome v1.4211 CSNK1E Zornitza Stark Publications for gene: CSNK1E were set to 30488659
Mendeliome v1.4210 CSNK1E Zornitza Stark edited their review of gene: CSNK1E: Added comment: PMID 40751262 identifies a heterozygous CGG repeat expansion in the 5′‑UTR of CSNK1E associated with progressive myoclonic epilepsy, ataxia and cognitive decline onset at 10 years, showing incomplete penetrance (present in unaffected sister).; Changed publications: 30488659, 40751262
Mendeliome v1.4210 MFN2 Sangavi Sivagnanasundram reviewed gene: MFN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hereditary motor and sensory neuropathy MONDO:0015358, multiple symmetric lipomatosis with partial lipodystrophy MONDO:1060153; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4210 PAX3 Sangavi Sivagnanasundram reviewed gene: PAX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7726174; Phenotypes: Waardenburg syndrome MONDO:0018094; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4210 PDHB Sangavi Sivagnanasundram Publications for gene: PDHB were set to
Mendeliome v1.4209 MASP2 Sangavi Sivagnanasundram Publications for gene: MASP2 were set to
Mendeliome v1.4208 PAICS Sangavi Sivagnanasundram reviewed gene: PAICS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: PAICS deficiency MONDO:0859003; Mode of inheritance: None
Mendeliome v1.4208 OXA1L Sangavi Sivagnanasundram reviewed gene: OXA1L: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: OXA1L-related combined oxidative phosphorylation deficiency MONDO:0000732; Mode of inheritance: None
Mendeliome v1.4208 GDF5 Lucy Spencer Phenotypes for gene: GDF5 were changed from Type A1C brachydactyly (MIM#615072); Type A2 brachydactyly, (MIM#112600); Type C brachydactyly (MIM#113100); Grebe type chondrodysplasia (MIM#200700); Du Pan syndrome (MIM#228900); Multiple synostoses syndrome 2 (MIM#610017); Proximal Symphalangism 1B (MIM#615298) to Brachydactyly MONDO:0021004, GDF5-related; Acromelic dysplasia MONDO:0019695, GDF5-related; Type A1C brachydactyly (MIM#615072); Type A2 brachydactyly, (MIM#112600); Type C brachydactyly (MIM#113100); Grebe type chondrodysplasia (MIM#200700); Du Pan syndrome (MIM#228900); Multiple synostoses syndrome 2 (MIM#610017); Proximal Symphalangism 1B (MIM#615298)
Mendeliome v1.4207 GDF5 Lucy Spencer reviewed gene: GDF5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Brachydactyly MONDO:0021004, GDF5-related, Acromelic dysplasia MONDO:0019695, GDF5-related; Mode of inheritance: None
Mendeliome v1.4207 GNAS Lucy Spencer Phenotypes for gene: GNAS were changed from Osseous heteroplasia, progressive (166350) AD; Pituitary adenoma 3, multiple types, somatic (617686); Pseudohypoparathyroidism Ia (103580) AD; Pseudohypoparathyroidism Ib (603233) AD; Pseudohypoparathyroidism Ic (612462) AD; Pseudopseudohypoparathyroidism (612463) to Disorder of GNAS inactivation MONDO:0800466; Osseous heteroplasia, progressive (166350) AD; Pituitary adenoma 3, multiple types, somatic (617686); Pseudohypoparathyroidism Ia (103580) AD; Pseudohypoparathyroidism Ib (603233) AD; Pseudohypoparathyroidism Ic (612462) AD; Pseudopseudohypoparathyroidism (612463)
Mendeliome v1.4206 GNAS Lucy Spencer reviewed gene: GNAS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Disorder of GNAS inactivation MONDO:0800466; Mode of inheritance: None
Mendeliome v1.4206 KRT14 Lucy Spencer Phenotypes for gene: KRT14 were changed from Epidermolysis bullosa simplex, recessive 1, 601001; Dermatopathia pigmentosa reticularis, 125595; Epidermolysis bullosa simplex, Dowling-Meara type, 131760; Epidermolysis bullosa simplex, Koebner type, 131900; Epidermolysis bullosa simplex, Weber-Cockayne type, 131800; Naegeli-Franceschetti-Jadassohn syndrome, 161000 to Epidermolysis bullosa MONDO:0006541, KRT14-related; Epidermolysis bullosa simplex, recessive 1, 601001; Dermatopathia pigmentosa reticularis, 125595; Epidermolysis bullosa simplex, Dowling-Meara type, 131760; Epidermolysis bullosa simplex, Koebner type, 131900; Epidermolysis bullosa simplex, Weber-Cockayne type, 131800; Naegeli-Franceschetti-Jadassohn syndrome, 161000
Mendeliome v1.4205 KRT14 Lucy Spencer reviewed gene: KRT14: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa MONDO:0006541, KRT14-related; Mode of inheritance: None
Mendeliome v1.4205 MYT1 Sangavi Sivagnanasundram reviewed gene: MYT1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: MYT1-related oculoauriculovertebral spectrum MONDO:0007712; Mode of inheritance: None
Mendeliome v1.4205 KRT10 Lucy Spencer Phenotypes for gene: KRT10 were changed from Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis with confetti, MIM#609165; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM#607602 to Ichthyosis MONDO:0019269, KRT10-related; Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis with confetti, MIM#609165; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM#607602
Mendeliome v1.4204 KRT10 Lucy Spencer reviewed gene: KRT10: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis MONDO:0019269, KRT10-related; Mode of inheritance: None
Mendeliome v1.4204 KRT1 Lucy Spencer Phenotypes for gene: KRT1 were changed from Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM# 607602; Ichthyosis histrix, Curth-Macklin type, MIM# 146590; Palmoplantar keratoderma, epidermolytic, MIM# 144200; Palmoplantar keratoderma, nonepidermolytic, MIM# 600962 to Ichthyosis MONDO:0019269, KRT1-related; Palmoplantar keratosis MONDO:0006590, KRT1-related; Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM# 607602; Ichthyosis histrix, Curth-Macklin type, MIM# 146590; Palmoplantar keratoderma, epidermolytic, MIM# 144200; Palmoplantar keratoderma, nonepidermolytic, MIM# 600962
Mendeliome v1.4203 KRT1 Lucy Spencer reviewed gene: KRT1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis MONDO:0019269, KRT1-related, Palmoplantar keratosis MONDO:0006590, KRT1-related; Mode of inheritance: None
Mendeliome v1.4203 KRT5 Lucy Spencer Phenotypes for gene: KRT5 were changed from Dowling-Degos disease 1, MIM# 179850; Epidermolysis bullosa simplex-MCR, MIM# 609352; Epidermolysis bullosa simplex-MP 131960; Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760; Epidermolysis bullosa simplex, Koebner type, MIM# 131900; Epidermolysis bullosa simplex, recessive 1, MIM# 601001; Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800 to Epidermolysis bullosa MONDO:0006541, KRT5-related; Dowling-Degos disease 1, MIM# 179850; Epidermolysis bullosa simplex-MCR, MIM# 609352; Epidermolysis bullosa simplex-MP 131960; Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760; Epidermolysis bullosa simplex, Koebner type, MIM# 131900; Epidermolysis bullosa simplex, recessive 1, MIM# 601001; Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800
Mendeliome v1.4202 KRT5 Lucy Spencer reviewed gene: KRT5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa MONDO:0006541, KRT5-related; Mode of inheritance: None
Mendeliome v1.4202 MYADML2 Sangavi Sivagnanasundram reviewed gene: MYADML2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: MYADML2-related connective tissue disroder MONDO:0003900; Mode of inheritance: None
Mendeliome v1.4202 SKAP2 Zornitza Stark Marked gene: SKAP2 as ready
Mendeliome v1.4202 SKAP2 Zornitza Stark Gene: skap2 has been classified as Red List (Low Evidence).
Mendeliome v1.4202 SKAP2 Zornitza Stark gene: SKAP2 was added
gene: SKAP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SKAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SKAP2 were set to 40771593; 34172489
Phenotypes for gene: SKAP2 were set to Inborn error of immunity, MONDO:0003778
Review for gene: SKAP2 was set to RED
Added comment: PMID 34172489 reports a de novo heterozygous SKAP2 missense variant (c.457G>A, p.Gly153Arg) in a child with childhood‑onset type 1 diabetes and multiple autoimmune disorders; functional studies in THP‑1 macrophages, patient‑derived macrophages and neutrophils show constitutive SKAP2 activation and hyper‑integrin signaling. The same variant was later described in PMID 40771593.
Sources: Literature
Mendeliome v1.4201 NRDC Rylee Peters Classified gene: NRDC as Amber List (moderate evidence)
Mendeliome v1.4201 NRDC Rylee Peters Gene: nrdc has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4200 NRDC Rylee Peters gene: NRDC was added
gene: NRDC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654
Phenotypes for gene: NRDC were set to Neurodevelopmental disorder, MONDO:0700092, NRDC-related
Review for gene: NRDC was set to AMBER
Added comment: Two unrelated families reported with the same homozygous NMD-predicted frameshift variant. PMID: 41449824 describes two affected siblings with severe neurodevelopmental disorder (developmental delay, microcephaly, hypotonia, seizures, absent speech). PMID: 28017472 reports one individual with severe global developmental delay, ataxia, progressive neurodegeneration, and acquired microcephaly.

PMID: 34582790 describes an additional homozygous splice variant (NRDC c.3081-2A>G) in an infant with developmental delay, ventricular dilatation and large nevi; however, the individual was also homozygous for a pathogenic NANS missense variant (c.635T>C; p.I212T), which has an established gene–disease association.

PMID: 19935654 | Nrd1−/− mice show reduced brain size, thin cerebral cortex, central and peripheral hypomyelination, with motor impairment and cognitive deficits.
Sources: Literature
Mendeliome v1.4199 NNT Zornitza Stark Publications for gene: NNT were set to 22634753; 23474776; 25879317; 26070314; 27129361
Mendeliome v1.4198 NNT Zornitza Stark reviewed gene: NNT: Rating: RED; Mode of pathogenicity: None; Publications: 40709434; Phenotypes: Familial sebaceous hyperplasia, MONDO:0011130, NNT-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4198 ARCN1 Zornitza Stark changed review comment from: At least 8 unrelated families reported with heterozygous variants.; to: At least 14 individuals reported, summarised in PMID 35300924. Intrauterine growth restriction, micrognathia, and short stature were present in all patients. Other common features included prematurity (11/15, 73.3%), developmental delay (10/14, 71.4%), genitourinary malformations in males (6/8, 75%), and microcephaly (12/15, 80%).
Mendeliome v1.4198 ARCN1 Zornitza Stark Mode of inheritance for gene: ARCN1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4197 ARCN1 Zornitza Stark changed review comment from: 4 unrelated families reported with heterozygous variants.; to: At least 8 unrelated families reported with heterozygous variants.
Mendeliome v1.4197 ARCN1 Zornitza Stark edited their review of gene: ARCN1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4197 ARCN1 Zornitza Stark Deleted their comment
Mendeliome v1.4197 ARCN1 Zornitza Stark Publications for gene: ARCN1 were set to 27476655; 33154040
Mendeliome v1.4196 ARCN1 Zornitza Stark Mode of inheritance for gene: ARCN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4195 ARCN1 Zornitza Stark changed review comment from: 4 unrelated families reported.; to: 4 unrelated families reported with heterozygous variants.
Mendeliome v1.4195 ARCN1 Zornitza Stark edited their review of gene: ARCN1: Added comment: PMID 35300924 reports 14 individuals (9 post‑natal, 5 fetuses) from 3 unrelated families with biallelic loss‑of‑function ARCN1 variants. Core phenotype includes intrauterine growth restriction, micrognathia, short stature, rhizomelic shortening, microcephaly, variable developmental delay/intellectual disability, genitourinary anomalies in males, cataracts, transient liver dysfunction/glycosylation abnormalities, and rare complications such as hepatoblastoma. Functional assays show defective type I collagen transport and abnormal N‑glycan profiles.; Changed publications: 27476655, 33154040, 35300924; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4195 YWHAZ Zornitza Stark Publications for gene: YWHAZ were set to 36001342; 31024343; 35143101; 35501409; 22124272; 26207352
Mendeliome v1.4194 YWHAZ Zornitza Stark edited their review of gene: YWHAZ: Added comment: Further invidividual reported as part of a large CFC cohort PMID 40692796, missense variant, limited further information.; Changed publications: 36001342, 31024343, 35143101, 35501409, 22124272, 26207352, 40692796
Mendeliome v1.4194 PRKCH Zornitza Stark Phenotypes for gene: PRKCH were changed from to Alzheimer disease, MONDO:0004975, PRKCH-related
Mendeliome v1.4193 PRKCH Zornitza Stark Publications for gene: PRKCH were set to
Mendeliome v1.4192 PRKCH Zornitza Stark Mode of inheritance for gene: PRKCH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4191 PRKCH Zornitza Stark reviewed gene: PRKCH: Rating: RED; Mode of pathogenicity: None; Publications: 40591711; Phenotypes: Alzheimer disease, MONDO:0004975, PRKCH-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4191 NXF3 Zornitza Stark edited their review of gene: NXF3: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.4191 NXF3 Zornitza Stark Marked gene: NXF3 as ready
Mendeliome v1.4191 NXF3 Zornitza Stark Gene: nxf3 has been classified as Red List (Low Evidence).
Mendeliome v1.4191 NXF3 Zornitza Stark Mode of inheritance for gene: NXF3 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.4190 NXF3 Zornitza Stark gene: NXF3 was added
gene: NXF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NXF3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: NXF3 were set to 40624043
Phenotypes for gene: NXF3 were set to Spermatogenic failure, MONDO:0004983, NXF3-related
Review for gene: NXF3 was set to RED
Added comment: PMID 40624043 reports a single individual with a hemizygous stop‑gain NXF3 variant inherited from a heterozygous carrier mother, presenting with severe oligoasthenoteratozoospermia. Functional studies show a truncated protein lacking the NTF2‑like domain, loss of binding to NXT2, and absence of NXF3 staining in sperm, supporting a loss‑of‑function mechanism.
Sources: Literature
Mendeliome v1.4189 TTC37 Zornitza Stark changed review comment from: Characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhoea in infancy requiring total parenteral nutrition, and immunodepression. Over 20 families reported.; to: Characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhoea in infancy requiring total parenteral nutrition, and immunodepression. Over 20 families reported.

New HGNC approved name is SKIC3.
Mendeliome v1.4189 TTC37 Zornitza Stark Tag new gene name tag was added to gene: TTC37.
Mendeliome v1.4189 LRRC6 Zornitza Stark changed review comment from: More than 10 unrelated families reported.

Newe HGNC approved name is DNAAF11.; to: More than 10 unrelated families reported.

New HGNC approved name is DNAAF11.
Mendeliome v1.4189 LRRC6 Zornitza Stark changed review comment from: More than 10 unrelated families reported.; to: More than 10 unrelated families reported.

Newe HGNC approved name is DNAAF11.
Mendeliome v1.4189 LRRC6 Zornitza Stark Tag new gene name tag was added to gene: LRRC6.
Mendeliome v1.4189 SUN5 Zornitza Stark Marked gene: SUN5 as ready
Mendeliome v1.4189 SUN5 Zornitza Stark Gene: sun5 has been classified as Green List (High Evidence).
Mendeliome v1.4189 SUN5 Zornitza Stark Classified gene: SUN5 as Green List (high evidence)
Mendeliome v1.4189 SUN5 Zornitza Stark Gene: sun5 has been classified as Green List (High Evidence).
Mendeliome v1.4188 SUN5 Zornitza Stark gene: SUN5 was added
gene: SUN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUN5 were set to 34159570; 33671757; 27640305
Phenotypes for gene: SUN5 were set to Spermatogenic failure, MONDO:0004983, SUN5-related
Review for gene: SUN5 was set to GREEN
Added comment: SUN5 encodes a testis‑specific SUN‑domain protein that anchors the sperm head to the tail. Multiple independent studies have identified biallelic loss‑of‑function SUN5 variants in >30 individuals with acephalic spermatozoa syndrome. Functional studies—including Western blot, immunofluorescence, Sun5 knockout mouse models, HeLa splicing assays, Y2H/GST pull‑down and proteasome‑inhibition rescue—demonstrate loss of SUN5 protein and disrupted head‑tail coupling, supporting loss‑of‑function as the disease mechanism.
Sources: Literature
Mendeliome v1.4187 SPNS1 Zornitza Stark Publications for gene: SPNS1 were set to 40608416
Mendeliome v1.4186 SPNS1 Zornitza Stark Classified gene: SPNS1 as Green List (high evidence)
Mendeliome v1.4186 SPNS1 Zornitza Stark Gene: spns1 has been classified as Green List (High Evidence).
Mendeliome v1.4185 SPNS1 Zornitza Stark reviewed gene: SPNS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38451736; Phenotypes: Lysosomal disorder, SPNS1-related, MONDO:0002561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4185 MTSS1L Zornitza Stark Tag new gene name tag was added to gene: MTSS1L.
Mendeliome v1.4185 MTSS1L Zornitza Stark Publications for gene: MTSS1L were set to PMID: 36067766
Mendeliome v1.4184 MTSS1L Zornitza Stark reviewed gene: MTSS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 39890443, 40698928; Phenotypes: Intellectual developmental disorder with ocular anomalies and distinctive facial features, MIM# 620086; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4184 CSMD3 Zornitza Stark reviewed gene: CSMD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35245678; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.4184 KRT8 Bryony Thompson Mode of inheritance for gene: KRT8 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4183 SF3B1 Zornitza Stark Phenotypes for gene: SF3B1 were changed from complex neurodevelopmental disorder MONDO:0100038 to complex neurodevelopmental disorder MONDO:0100038, SF3B1-related
Mendeliome v1.4182 SF3B1 Zornitza Stark Publications for gene: SF3B1 were set to
Mendeliome v1.4181 SF3B1 Zornitza Stark reviewed gene: SF3B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41577671; Phenotypes: complex neurodevelopmental disorder MONDO:0100038, SF3B1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4181 TUBB1 Zornitza Stark changed review comment from: PMIDs 30446499, 31642429 and 40071799 -- more than 5 individuals reported with congenital hypothyroidism and mono-allelic variants in TUBB1. One individual with bi-allelic. Unclear if this is a separate association at present.; to: PMIDs 30446499, 31642429 and 40071799 -- more than 5 individuals reported with congenital hypothyroidism and mono-allelic variants in TUBB1. One individual with bi-allelic. Unclear if this is a separate association at present. Also note relatively high gnomAD counts for the reported variants, hence AMBER for association with hypothyroidism.
Mendeliome v1.4181 TUBB1 Zornitza Stark edited their review of gene: TUBB1: Changed rating: AMBER
Mendeliome v1.4181 TUBB1 Zornitza Stark Phenotypes for gene: TUBB1 were changed from Macrothrombocytopenia, autosomal dominant, TUBB1-related, OMIM #613112; MONDO:0013141 to Macrothrombocytopenia, autosomal dominant, TUBB1-related, OMIM #613112; MONDO:0013141; Hypothyroidism
Mendeliome v1.4180 TUBB1 Zornitza Stark Publications for gene: TUBB1 were set to 32757236; 31565851; 29333906; 18849486
Mendeliome v1.4179 TUBB1 Zornitza Stark changed review comment from: PMIDs 30446499, 31642429 and 40071799 -- more than 5 individuals reported with congenital hypothyroidism and mono-allelic variants in TUBB1. One individual with bi-allelic.; to: PMIDs 30446499, 31642429 and 40071799 -- more than 5 individuals reported with congenital hypothyroidism and mono-allelic variants in TUBB1. One individual with bi-allelic. Unclear if this is a separate association at present.
Mendeliome v1.4179 TUBB1 Zornitza Stark Deleted their comment
Mendeliome v1.4179 TUBB1 Zornitza Stark edited their review of gene: TUBB1: Added comment: PMIDs 30446499, 31642429 and 40071799 -- more than 5 individuals reported with congenital hypothyroidism and mono-allelic variants in TUBB1. One individual with bi-allelic.; Changed publications: 30446499, 31642429, 40071799; Changed phenotypes: Macrothrombocytopenia, autosomal dominant, TUBB1-related, OMIM #613112, MONDO:0013141, Hypothyroidism
Mendeliome v1.4179 SAG Zornitza Stark changed review comment from: Association with AD RP: PMID: 28549094 12 Hispanic families with 20 affecteds sharing the same haplotype suggestive of dominant founder mutation PMID: 33047631 1x Australian family *all sharing the same variant Cys147Phe.

Association with AR RP: Recurrent homozygous 1-bp deletion, 1147delA, identified in multiple Japanese families -- in some, affected individuals had Oguchi disease, suggesting the two conditions are part of a spectrum.; to: Association with AD RP: PMID: 28549094 12 Hispanic families with 20 affecteds sharing the same haplotype suggestive of dominant founder mutation PMID: 33047631 1x Australian family *all sharing the same variant Cys147Phe.

Association with AR RP: Recurrent homozygous 1-bp deletion, 1147delA, identified in multiple Japanese families -- in some, affected individuals had Oguchi disease, suggesting the two conditions are part of a spectrum.

Associations with RP are AMBER due to the recurrent nature of the variants.
Mendeliome v1.4179 SAG Zornitza Stark Phenotypes for gene: SAG were changed from Oguchi disease-1, MIM# 258100; Retinitis pigmentosa 47, MIM# 613758 to Oguchi disease-1, MIM# 258100; Retinitis pigmentosa 47, autosomal recessive MIM# 613758; Retinitis pigmentosa 96, autosomal dominant, MIM# 620228
Mendeliome v1.4178 SAG Zornitza Stark Publications for gene: SAG were set to 7670478; 9565049; 15234147; 28549094; 33047631
Mendeliome v1.4177 SAG Zornitza Stark Mode of inheritance for gene: SAG was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4176 SAG Zornitza Stark edited their review of gene: SAG: Added comment: Association with AD RP: PMID: 28549094 12 Hispanic families with 20 affecteds sharing the same haplotype suggestive of dominant founder mutation PMID: 33047631 1x Australian family *all sharing the same variant Cys147Phe.

Association with AR RP: Recurrent homozygous 1-bp deletion, 1147delA, identified in multiple Japanese families -- in some, affected individuals had Oguchi disease, suggesting the two conditions are part of a spectrum.; Changed publications: 7670478, 9565049, 15234147, 28549094, 33047631, 9565049, 31257036; Changed phenotypes: Oguchi disease-1, MIM# 258100, Retinitis pigmentosa 47, autosomal recessive MIM# 613758, Retinitis pigmentosa 96, autosomal dominant, MIM# 620228; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4176 RNF213 Zornitza Stark changed review comment from: Five unrelated adults (four males, one female; median diagnosis age 26 y) reported with peripheral pulmonary artery stenosis (PPAS) presenting with pulmonary hypertension, a characteristic string‑of‑beads pattern on angiography and multiple extracranial vascular lesions. All five were homozygous for the missense RNF213 p.Arg4810Lys (c.14429G>A) variant; three also had Moyamoya disease (MMD).; to: Five unrelated adults (four males, one female; median diagnosis age 26 y) reported with peripheral pulmonary artery stenosis (PPAS) presenting with pulmonary hypertension, a characteristic string‑of‑beads pattern on angiography and multiple extracranial vascular lesions. All five were homozygous for the missense RNF213 p.Arg4810Lys (c.14429G>A) variant; three also had Moyamoya disease (MMD).

RED for this MOI/association.
Mendeliome v1.4176 RNF213 Zornitza Stark reviewed gene: RNF213: Rating: RED; Mode of pathogenicity: None; Publications: 28962888; Phenotypes: Moyamoya disease, MONDO:0016820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4176 OTOG Zornitza Stark Publications for gene: OTOG were set to 29800624; 23122587
Mendeliome v1.4175 OTOG Zornitza Stark reviewed gene: OTOG: Rating: GREEN; Mode of pathogenicity: None; Publications: 30139988, 31645975, 32048449, 32244554, 32860223, 34118384, 35248088, 38894825, 39858607, 40389292, 40565546, 33136635, 38519595, 40565546; Phenotypes: Deafness, autosomal recessive 18B - MIM#614945; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4175 MYO5B Zornitza Stark Phenotypes for gene: MYO5B were changed from Microvillus inclusion disease, MIM# 251850; Cholestasis to Microvillus inclusion disease, MIM# 251850; Cholestasis, progressive familial intrahepatic, 10, MIM# 619868
Mendeliome v1.4174 MYO5B Zornitza Stark Publications for gene: MYO5B were set to 30564347; 29266534; 28027573; 27532546
Mendeliome v1.4173 MYO5B Zornitza Stark edited their review of gene: MYO5B: Added comment: PMID 33525641 summarises data on 114 individuals with bi-allelic variants in MYO5B: (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED).; Changed publications: 30564347, 29266534, 28027573, 27532546, 33525641; Changed phenotypes: Microvillus inclusion disease, MIM# 251850, Cholestasis, progressive familial intrahepatic, 10, MIM# 619868
Mendeliome v1.4173 HSPB1 Zornitza Stark Mode of inheritance for gene: HSPB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4172 HSPB1 Zornitza Stark changed review comment from: Multiple families reported, functional data. Different patterns of neuropathy described.; to: Multiple AD families reported, functional data. Different patterns of neuropathy described.
Mendeliome v1.4172 HSPB1 Zornitza Stark edited their review of gene: HSPB1: Added comment: PMID 33943041: two unrelated individuals with homozygous missense variants, p.S135F and p.R136L, and CMT. Both variants already reported as pathogenic in the heterozygous state. Third compound het individual reported in 35328016.; Changed publications: 21785432, 15122254, 18832141, 32639100, 32334137, 33943041, 35328016; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4172 GPAA1 Zornitza Stark Phenotypes for gene: GPAA1 were changed from Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810 to Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810; Vascular malformation, MONDO:0024291, GPAA1-relatedVascular malformation, MONDO:0024291, GPAA1-related
Mendeliome v1.4171 GPAA1 Zornitza Stark Publications for gene: GPAA1 were set to 29100095
Mendeliome v1.4170 GPAA1 Zornitza Stark Mode of inheritance for gene: GPAA1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4169 GPAA1 Zornitza Stark changed review comment from: PMID 32533362 reports a single family with a GPAA1 missense (c.968A > G; p.Asn323Ser) segregating in 4 affected individuals and not among 6 unaffected individuals. Affected individuals presented with cavernous venous malformation, capillary malformation and infantile haemangioma. Also, supporting in vitro functional assays for the variant impacting function and a gpaa1-deficient zebrafish model displaying several types of developmental defects as well as vascular dysplasia.; to: PMID 32533362 reports a single family with a GPAA1 missense (c.968A > G; p.Asn323Ser) segregating in 4 affected individuals and not among 6 unaffected individuals. Affected individuals presented with cavernous venous malformation, capillary malformation and infantile haemangioma. Also, supporting in vitro functional assays for the variant impacting function and a gpaa1-deficient zebrafish model displaying several types of developmental defects as well as vascular dysplasia.

AMBER for this MOI.
Mendeliome v1.4169 GPAA1 Zornitza Stark edited their review of gene: GPAA1: Changed phenotypes: Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810, Vascular malformation, MONDO:0024291, GPAA1-related
Mendeliome v1.4169 GPAA1 Zornitza Stark edited their review of gene: GPAA1: Added comment: PMID 32533362 reports a single family with a GPAA1 missense (c.968A > G; p.Asn323Ser) segregating in 4 affected individuals and not among 6 unaffected individuals. Affected individuals presented with cavernous venous malformation, capillary malformation and infantile haemangioma. Also, supporting in vitro functional assays for the variant impacting function and a gpaa1-deficient zebrafish model displaying several types of developmental defects as well as vascular dysplasia.; Changed publications: 29100095, 32533362; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4169 FLI1 Zornitza Stark Publications for gene: FLI1 were set to 10891501; 10981960; 24100448; 28255014; 26316623
Mendeliome v1.4168 FLI1 Zornitza Stark Mode of inheritance for gene: FLI1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4167 FLI1 Zornitza Stark reviewed gene: FLI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24100448, 28255014, 26316623, 26494917; Phenotypes: Bleeding disorder, platelet-type, 21, MIM# 617443; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4167 F12 Zornitza Stark Phenotypes for gene: F12 were changed from Hereditary angioedema type 3 MONDO:0012526 to Factor XII deficiency, MIM# 234000; Hereditary angioedema type 3 MONDO:0012526
Mendeliome v1.4166 F12 Zornitza Stark Publications for gene: F12 were set to 26193639; 16638441; 17381464; 21849258; 17186468; 19178938; 30463937; 23994767
Mendeliome v1.4165 F12 Zornitza Stark Mode of inheritance for gene: F12 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4164 F12 Zornitza Stark reviewed gene: F12: Rating: GREEN; Mode of pathogenicity: None; Publications: 8528215, 10361128; Phenotypes: Factor XII deficiency, MIM# 234000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4164 VPS51 Zornitza Stark Publications for gene: VPS51 were set to 30624672; 31207318
Mendeliome v1.4163 VPS51 Zornitza Stark edited their review of gene: VPS51: Changed publications: 40565173, 30624672, 31207318, 40176246
Mendeliome v1.4163 VPS51 Zornitza Stark edited their review of gene: VPS51: Changed publications: 40565173
Mendeliome v1.4163 VPS51 Zornitza Stark Classified gene: VPS51 as Green List (high evidence)
Mendeliome v1.4163 VPS51 Zornitza Stark Gene: vps51 has been classified as Green List (High Evidence).
Mendeliome v1.4162 VPS51 Zornitza Stark edited their review of gene: VPS51: Added comment: PMID 40176246 Reports another individual with autosomal recessive homozygous in-frame duplication in VPS51 (p.Lys126_Met132dup) presenting with severe global developmental delay, microcephaly, hypotonia, hypomyelination, and cerebral and cerebellar atrophy. No functional studies performed; variant absent from gnomAD.

PMID 40565173 reports 2 affected individuals another family with a homozygous missense variant NM_013265.4:c.1511C>T (p.Thr504Met) in VPS51. The siblings presented with developmental delay, severe intellectual disability, microcephaly, thin corpus callosum, epilepsy, hearing loss and dysphagia. Biparental inheritance demonstrated. Functional assays in patient fibroblasts showed reduced VPS51 mRNA and protein levels, altered autophagy marker expression (LC3B, p62), and increased mitochondria‑lysosome contacts, supporting a loss‑of‑function mechanism.; Changed rating: GREEN; Changed publications: 30624672, 31207318, 40176246; Changed phenotypes: Pontocerebellar hypoplasia, type 13, MIM# 618606
Mendeliome v1.4162 SPTSSA Zornitza Stark Publications for gene: SPTSSA were set to 36718090
Mendeliome v1.4161 SPTSSA Zornitza Stark changed review comment from: Another individual with heterozygous de novo missense c.152C>T (p.Thr51Ile) reported, same variant, no change in rating.; to: Another individual with heterozygous de novo missense c.152C>T (p.Thr51Ile) reported, same variant, no change in rating, AMBER for both MOI.
Mendeliome v1.4161 SPTSSA Zornitza Stark edited their review of gene: SPTSSA: Added comment: Another individual with heterozygous de novo missense c.152C>T (p.Thr51Ile) reported, same variant, no change in rating.; Changed publications: 40533086
Mendeliome v1.4161 MYL1 Zornitza Stark Publications for gene: MYL1 were set to 30215711
Mendeliome v1.4160 MYL1 Zornitza Stark Classified gene: MYL1 as Green List (high evidence)
Mendeliome v1.4160 MYL1 Zornitza Stark Gene: myl1 has been classified as Green List (High Evidence).
Mendeliome v1.4159 MYL1 Zornitza Stark reviewed gene: MYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40488356; Phenotypes: Myopathy, congenital, with fast-twitch (type II) fiber atrophy MIM#618414; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4159 IL6R Zornitza Stark Publications for gene: IL6R were set to 31235509
Mendeliome v1.4158 IL6R Zornitza Stark Classified gene: IL6R as Green List (high evidence)
Mendeliome v1.4158 IL6R Zornitza Stark Gene: il6r has been classified as Green List (High Evidence).
Mendeliome v1.4157 IL6R Zornitza Stark edited their review of gene: IL6R: Changed rating: GREEN
Mendeliome v1.4157 IL6R Zornitza Stark edited their review of gene: IL6R: Added comment: PMID 40536180 reports 7 individuals from 7 families with a homozygous missense c.G494C (p.Cys165Ser) variant in IL6R, presenting with childhood‑onset recurrent respiratory infections, pneumonia, elevated IgE, normal CRP, and no early bronchiectasis. All patients received monthly IVIG; two required inhaled corticosteroids.

PMID 39277818 reports 4 individuals from 2 families with autosomal recessive loss‑of‑function homozygous nonsense variant c.284C>G (p.Ser95Ter) presenting with childhood‑onset cold abscesses, recurrent staphylococcal skin and sinopulmonary infections, high serum IgE, eosinophilia, atopic dermatitis, reduced Th17 cells and impaired STAT3 phosphorylation after IL‑6 stimulation. Functional assays demonstrate defective IL‑6 signalling. All patients are on cotrimoxazole prophylaxis with stable clinical course.; Changed publications: 31235509, 39277818, 40536180
Mendeliome v1.4157 IL17RD Zornitza Stark edited their review of gene: IL17RD: Changed rating: RED
Mendeliome v1.4157 SEC31A Zornitza Stark Publications for gene: SEC31A were set to PMID: 30464055; 40508110
Mendeliome v1.4156 SEC31A Zornitza Stark Classified gene: SEC31A as Green List (high evidence)
Mendeliome v1.4156 SEC31A Zornitza Stark Gene: sec31a has been classified as Green List (High Evidence).
Mendeliome v1.4155 SEC31A Zornitza Stark commented on gene: SEC31A: Functional data from PMID 30464055: knockdown SEC31A Drosophila had defective brains and early lethality. In line with SEC31A encoding one of the two coating layers comprising the Coat protein complex II (COP-II) complex, trafficking newly synthesised proteins from the endoplasmic reticulum (ER) to the Golgi, CRISPR/Cas9-mediated SEC31A null mutant cells demonstrated reduced viability through upregulation of ER-stress pathways.
Mendeliome v1.4155 SEC31A Zornitza Stark edited their review of gene: SEC31A: Added comment: PMID 39725565: Reports another individual from unrelated family with a homozygous splice‑acceptor loss‑of‑function variant (c.14351G>A) presenting with lethal neurodevelopmental disorder, dysmorphic facial features, brain anomalies, and severe skeletal defects. RT‑PCR on patient and carrier parents blood samples shows exon 12 skipping and markedly reduced SEC31A transcript, supporting loss‑of‑function.; Changed rating: GREEN; Changed publications: 30464055, 40508110, 39725565; Changed phenotypes: Halperin-Birk syndrome, MIM# 618651
Mendeliome v1.4155 HEY2 Zornitza Stark Classified gene: HEY2 as Amber List (moderate evidence)
Mendeliome v1.4155 HEY2 Zornitza Stark Gene: hey2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4154 HEY2 Zornitza Stark edited their review of gene: HEY2: Changed rating: AMBER
Mendeliome v1.4154 LGI1 Zornitza Stark Phenotypes for gene: LGI1 were changed from Epilepsy, familial temporal lobe, 1, MIM# 6000512; Developmental and epileptic encephalopathy MONDO:0100062, LGI1-related to Epilepsy, familial temporal lobe, 1, MIM# 6000512; Developmental and epileptic encephalopathy 121, MIM# 621475
Mendeliome v1.4153 LGI1 Zornitza Stark reviewed gene: LGI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 121, MIM# 621475; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4153 PLXNA1 Lucy Spencer changed review comment from: All 3 de novo missense variants in Dworschak et al. (2021) are present in gnomad v4 with 21, 2 and 4 heterozygotes. There is an additional de novo patient in Park 2017 PMID: 28464511, however their variant is also present in gnomad v4 with 5 heterozygotes. There is no recent literature supporting the dominant association

The monoallelic assertion for this gene is now RED, still GREEN for biallelic; to: All 3 de novo missense variants in Dworschak et al. (2021) are present in gnomad v4 with 21, 2 and 4 heterozygotes. There is an additional de novo patient in Park 2017 PMID: 28464511, however their variant is also present in gnomad v4 with 5 heterozygotes. There is no recent literature supporting the dominant association

The monoallelic assertion for a neurodevelopmental disorder in this gene is now RED, still GREEN for biallelic
Mendeliome v1.4153 PLXNA1 Lucy Spencer edited their review of gene: PLXNA1: Changed publications: 34054129, 28464511, 28334861, 30467832, 34636164; Changed phenotypes: Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955, Hypogonadotropic hypogonadism MONDO:0018555, PLXNA1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4153 PLXNA1 Lucy Spencer Publications for gene: PLXNA1 were set to 34054129; 28464511
Mendeliome v1.4152 PLXNA1 Lucy Spencer Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955 to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955; Hypogonadotropic hypogonadism MONDO:0018555, PLXNA1-related
Mendeliome v1.4151 PLXNA1 Lucy Spencer Mode of inheritance for gene: PLXNA1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4150 PLXNA1 Lucy Spencer edited their review of gene: PLXNA1: Added comment: reported phenotype expansion for monoallelic Kallman syndrome:
PMIDs 28334861 13 families with Kallman syndrome, however only 3 of these variants (His684Tyr Lys1618Thr Cys1744Phe) are absent from gnomad, the rest have at least 6 hets and most have over 20 hets. in transfected cells His684Tyr, Lys1618Thr and some of the common missense variants were shown to result in reduced total amounts of protein. In a minigene assay Cys1744Phe which is at the last base of an exon was shown to cause intron 28 retention which would be out of frame. No variants in this study were noted to be de novo.

PMID: 30467832 10 missense variants identified in patients with hypogonadotropic hypogonadism. Again some of the reported missense have over 20 hets in gnomad but 5 of the variants are rare or absent Lys1451Arg, Ser1850Arg, Ile1701Val, Pro485Leu and Val536Ile. All of these variants were either inherited from a parent or inheritance was unknown, and 1 individual had a better diagnosis with a nonsense in FGFR1 while other patients had variants in other genes amber for HH. No variants in this study were noted to be de novo.

PMID: 34636164 another 10 missense variants identified in 11 families with hypogonadotropic hypogonadism. However, only 3 were not common in gnomad; Pro848Arg, Ala1106Val, and Ser1709Leu. Ala1106Val and Ser1709Leu were both inherited from unaffected mothers, and most patients in this study also had variants of interest in other genes. No variants in this study were noted to be de novo.

So at least 10 reports of variants that are rare/absent in gnomad with Kallman syndrome, all missense variants, most without segregation information or inherited from unaffected/unknown if affected parents. Some with a bit of functional work. Many patients also have variants of interest in other genes amber or green for the same phenotype. borderline amber/green; Changed rating: AMBER; Changed phenotypes: Hypogonadotropic hypogonadism MONDO:0018555, PLXNA1-related
Mendeliome v1.4150 LINGO4 Lucy Spencer Publications for gene: LINGO4 were set to PMID: 33098801
Mendeliome v1.4149 LINGO4 Lucy Spencer Phenotypes for gene: LINGO4 were changed from Developmental Delay, Intellectual disability, speech disorder to Neurodevelopmental disorder (MONDO:0700092), LINGO4-related
Mendeliome v1.4148 SRP72 Lucy Spencer edited their review of gene: SRP72: Changed publications: 40922878, 37176611, 41472573, 40510848, 41142505
Mendeliome v1.4148 SRP72 Lucy Spencer changed review comment from: PMID: 41142505 15yo with thrombocytopenia, mild anemia with macrocytosis and mild leukopenia. found to have a paternally inherited missense in SRP72 (2 hets in gnomad) along with maternally inherited missense (absent from gnomad) in TINF2 and deep intronic variant in TERT (absent from gnomad).

PMID: 41472573 6yo boy with aplastic anemia, pancytopenia and leukopenia, thrombocytopenia and reduced red cell count. Found to have a de novo canonical splice variant c.1502+1G>A that has 63 hets in gnomad. RT-PCR showed retention of 2bp leading to an out of frame product.

PMID: 40510848 1 individual in a congenital neuropenia cohort with an SPR72 variant. Variant only listed in the supplementary material Trp474*, inheritance unknown, absent from gnomad

PMID: 37176611 4yo girl with repeated infections and severe neutropenia. Found to have a paternally inherited balanced translocation t(3;8)(p26;q21)c, as well as maternally inherited synonymous variant in SRP72 and missense in ANKRD26. The synonymous variant in this case has over 4000 homs in gnomad and is very unlikely to be contributing to the phenotype.

Only 1 compelling report in PMID: 40510848, however other NMD variants are present in gnomad with high het counts. borderline amber/green; to: PMID: 41142505 15yo with thrombocytopenia, mild anemia with macrocytosis and mild leukopenia. found to have a paternally inherited missense in SRP72 (2 hets in gnomad) along with maternally inherited missense (absent from gnomad) in TINF2 and deep intronic variant in TERT (absent from gnomad).

PMID: 41472573 6yo boy with aplastic anemia, pancytopenia and leukopenia, thrombocytopenia and reduced red cell count. Found to have a de novo canonical splice variant c.1502+1G>A that has 63 hets in gnomad. RT-PCR showed retention of 2bp leading to an out of frame product.

PMID: 40510848 1 individual in a congenital neuropenia cohort with an SPR72 variant. Variant only listed in the supplementary material Trp474*, inheritance unknown, absent from gnomad

PMID: 37176611 4yo girl with repeated infections and severe neutropenia. Found to have a paternally inherited balanced translocation t(3;8)(p26;q21)c, as well as maternally inherited synonymous variant in SRP72 and missense in ANKRD26. The synonymous variant in this case has over 4000 homs in gnomad and is very unlikely to be contributing to the phenotype.

Only 1 compelling report in PMID: 40510848, however other NMD variants are present in gnomad with high het counts. borderline amber/green
Mendeliome v1.4148 SRP72 Lucy Spencer Publications for gene: SRP72 were set to 22541560; 31254415; 40922878; 3717661; 41472573; 40510848; 41142505
Mendeliome v1.4147 SRP72 Lucy Spencer Publications for gene: SRP72 were set to 22541560; 31254415; 40922878
Mendeliome v1.4146 SRP72 Lucy Spencer edited their review of gene: SRP72: Added comment: PMID: 41142505 15yo with thrombocytopenia, mild anemia with macrocytosis and mild leukopenia. found to have a paternally inherited missense in SRP72 (2 hets in gnomad) along with maternally inherited missense (absent from gnomad) in TINF2 and deep intronic variant in TERT (absent from gnomad).

PMID: 41472573 6yo boy with aplastic anemia, pancytopenia and leukopenia, thrombocytopenia and reduced red cell count. Found to have a de novo canonical splice variant c.1502+1G>A that has 63 hets in gnomad. RT-PCR showed retention of 2bp leading to an out of frame product.

PMID: 40510848 1 individual in a congenital neuropenia cohort with an SPR72 variant. Variant only listed in the supplementary material Trp474*, inheritance unknown, absent from gnomad

PMID: 37176611 4yo girl with repeated infections and severe neutropenia. Found to have a paternally inherited balanced translocation t(3;8)(p26;q21)c, as well as maternally inherited synonymous variant in SRP72 and missense in ANKRD26. The synonymous variant in this case has over 4000 homs in gnomad and is very unlikely to be contributing to the phenotype.

Only 1 compelling report in PMID: 40510848, however other NMD variants are present in gnomad with high het counts. borderline amber/green; Changed publications: 40922878, 3717661, 41472573, 40510848, 41142505
Mendeliome v1.4146 ZNF185 Lucy Spencer edited their review of gene: ZNF185: Changed publications: 41404552, 39267058; Changed phenotypes: Azoospermia MONDO:0100459, ZNF185-related, Cerebrooculonasal syndrome MONDO:0011575, ZNF185-related
Mendeliome v1.4146 ZNF185 Lucy Spencer Publications for gene: ZNF185 were set to 39267058
Mendeliome v1.4145 ZNF185 Lucy Spencer Phenotypes for gene: ZNF185 were changed from Azoospermia MONDO:0100459, ZNF185-related to Azoospermia MONDO:0100459, ZNF185-related; Cerebrooculonasal syndrome MONDO:0011575, ZNF185-related
Mendeliome v1.4144 ZNF185 Lucy Spencer edited their review of gene: ZNF185: Added comment: PMID 41404552 describes a single female individual with cerebro‑oculo‑nasal syndrome and a de novo heterozygous X‑linked frameshift ZNF185. The proband presented with developmental delay, moderate ID, dysmorphic facial features, cleft lip/palate, nasal anomaly, CHD and anopthalmia. She was shown to have skewed X-inactivation 19:81, however it is not stated if the skewing was towards the allele with the variant. The variant in this individual (p.Gln102SerfsTer18) is NMD predicted and absent from gnomad, however there are at least 6 NMD variants present in gnomad as hemizygous (4 with over 4 hemis) all of which also have over 5 heterozygotes.; Changed publications: 41404552; Changed phenotypes: Cerebrooculonasal syndrome MONDO:0011575, ZNF185-related
Mendeliome v1.4144 ZNF185 Lucy Spencer gene: ZNF185 was added
gene: ZNF185 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF185 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ZNF185 were set to 39267058
Phenotypes for gene: ZNF185 were set to Azoospermia MONDO:0100459, ZNF185-related
Review for gene: ZNF185 was set to RED
Added comment: PMID 39267058 reports three unrelated individuals with autosomal recessive primary male infertility (all 3 had non-obstructive azoospermia). All 3 were hemizygous for different missense variants, one of which has 28 hemis and 38 hets in gnomad v4, and another has 6 hemis and 4 hets in gnomad v4. No functional or segregation evidence was provided to support the pathogenicity of these variants.
Sources: Literature
Mendeliome v1.4143 NLRP7 Zornitza Stark edited their review of gene: NLRP7: Changed rating: GREEN
Mendeliome v1.4143 NLRP7 Zornitza Stark changed review comment from: Two individuals reported with this phenotype and mono-allelic variants.; to: Five individuals reported with this phenotype and mono-allelic variants.
Mendeliome v1.4143 NLRP7 Zornitza Stark Phenotypes for gene: NLRP7 were changed from Hydatidiform mole, recurrent, 1 - MIM#231090 to Hydatidiform mole, recurrent, 1 - MIM#231090; Oocyte/zygote/embryo maturation arrest 25, MIM# 621471
Mendeliome v1.4142 NLRP7 Zornitza Stark Publications for gene: NLRP7 were set to 23201303; 23125094; 25097207; 26606510; 19650864; 23880596; 22770628; 26544189; 28428943; 21623199; 21439709; 33583041; 32055942; 19246479; 19066229; 34189227
Mendeliome v1.4141 NLRP7 Zornitza Stark Mode of inheritance for gene: NLRP7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4140 NLRP7 Zornitza Stark Classified gene: NLRP7 as Green List (high evidence)
Mendeliome v1.4140 NLRP7 Zornitza Stark Gene: nlrp7 has been classified as Green List (High Evidence).
Mendeliome v1.4139 NLRP7 Zornitza Stark reviewed gene: NLRP7: Rating: AMBER; Mode of pathogenicity: None; Publications: 37148315; Phenotypes: Oocyte/zygote/embryo maturation arrest 25, MIM# 621471; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4139 IMPG1 Bryony Thompson Mode of inheritance for gene: IMPG1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4138 IGF1 Bryony Thompson Mode of inheritance for gene: IGF1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4137 PCBP1 Zornitza Stark Marked gene: PCBP1 as ready
Mendeliome v1.4137 PCBP1 Zornitza Stark Gene: pcbp1 has been classified as Green List (High Evidence).
Mendeliome v1.4137 PCBP1 Zornitza Stark Classified gene: PCBP1 as Green List (high evidence)
Mendeliome v1.4137 PCBP1 Zornitza Stark Gene: pcbp1 has been classified as Green List (High Evidence).
Mendeliome v1.4136 UNC13C Zornitza Stark Marked gene: UNC13C as ready
Mendeliome v1.4136 UNC13C Zornitza Stark Gene: unc13c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4136 UNC13C Zornitza Stark Classified gene: UNC13C as Amber List (moderate evidence)
Mendeliome v1.4136 UNC13C Zornitza Stark Gene: unc13c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4135 OSR2 Zornitza Stark Marked gene: OSR2 as ready
Mendeliome v1.4135 OSR2 Zornitza Stark Gene: osr2 has been classified as Green List (High Evidence).
Mendeliome v1.4135 OSR2 Zornitza Stark Phenotypes for gene: OSR2 were changed from MONDO:0005497 to Skeletal dysplasia, MONDO:0018230, OSR2-related
Mendeliome v1.4134 OSR2 Zornitza Stark Classified gene: OSR2 as Green List (high evidence)
Mendeliome v1.4134 OSR2 Zornitza Stark Gene: osr2 has been classified as Green List (High Evidence).
Mendeliome v1.4133 OSR2 Zornitza Stark reviewed gene: OSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia, MONDO:0018230, OSR2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4133 GSPT2 Zornitza Stark Phenotypes for gene: GSPT2 were changed from Intellectual disability MONDO:0001071, GSPT2-related to Neurodevelopmental disorder, MONDO:0700092, GSPT2-related
Mendeliome v1.4132 GSPT2 Zornitza Stark Publications for gene: GSPT2 were set to 28414775
Mendeliome v1.4131 GSPT2 Zornitza Stark Classified gene: GSPT2 as Green List (high evidence)
Mendeliome v1.4131 GSPT2 Zornitza Stark Gene: gspt2 has been classified as Green List (High Evidence).
Mendeliome v1.4130 CCDC149 Zornitza Stark Marked gene: CCDC149 as ready
Mendeliome v1.4130 CCDC149 Zornitza Stark Gene: ccdc149 has been classified as Red List (Low Evidence).
Mendeliome v1.4130 CCDC149 Zornitza Stark gene: CCDC149 was added
gene: CCDC149 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC149 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC149 were set to 40459248
Phenotypes for gene: CCDC149 were set to Cryptorchidism, MONDO:0009047, CCDC149-related
Review for gene: CCDC149 was set to RED
Added comment: PMID 40459248 reports a single 8‑year‑old boy from a consanguineous family with bilateral cryptorchidism due to a homozygous nonsense CCDC149 variant (c.448C>T, p.Gln150Ter), biparental inheritance. Ccdc149 knockout mice recapitulate undescended testes and sperm abnormalities, supporting loss‑of‑function as the disease mechanism.
Sources: Literature
Mendeliome v1.4129 TFCP2L1 Zornitza Stark Phenotypes for gene: TFCP2L1 were changed from CAKUT, MONDO:0019719, TFGP2L1-related to Inherited renal tubular disease, MONDO:0015962, TFGP2L1-related
Mendeliome v1.4128 TFCP2L1 Zornitza Stark edited their review of gene: TFCP2L1: Changed phenotypes: Inherited renal tubular disease, MONDO:0015962, TFGP2L1-related
Mendeliome v1.4128 GDF2 Bryony Thompson Mode of inheritance for gene: GDF2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4127 LIPC Bryony Thompson Mode of inheritance for gene: LIPC was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4126 LIM2 Bryony Thompson Mode of inheritance for gene: LIM2 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4125 LIM2 Bryony Thompson Mode of inheritance for gene: LIM2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4124 SCN10A Chirag Patel changed review comment from: Comment on mode of pathogenicity: AD - GOF
AR - LOF; to: Episodic pain syndrome, familial, 2 MIM#615551 - AD - GOF (green)
Neurodevelopmental disorder (MONDO#0700092), SCN10A-related - AR - LOF (amber)
Mendeliome v1.4124 SCN10A Chirag Patel Deleted their comment
Mendeliome v1.4124 SCN10A Chirag Patel Phenotypes for gene: SCN10A were changed from s) Episodic pain syndrome, familial, 2 MIM#615551; Neurodevelopmental disorder (MONDO#0700092), SCN10A-related to Episodic pain syndrome, familial, 2 MIM#615551; Neurodevelopmental disorder (MONDO#0700092), SCN10A-related
Mendeliome v1.4123 SCN10A Chirag Patel Phenotypes for gene: SCN10A were changed from Episodic pain syndrome, familial, 2, MIM# 615551 to s) Episodic pain syndrome, familial, 2 MIM#615551; Neurodevelopmental disorder (MONDO#0700092), SCN10A-related
Mendeliome v1.4122 SCN10A Chirag Patel Publications for gene: SCN10A were set to 23115331; 33775738; 30731422; 30554136
Mendeliome v1.4121 SCN10A Chirag Patel Mode of inheritance for gene: SCN10A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4120 SCN10A Chirag Patel Added comment: Comment on mode of pathogenicity: AD - GOF
AR - LOF
Mendeliome v1.4120 SCN10A Chirag Patel Mode of pathogenicity for gene: SCN10A was changed from to Other
Mendeliome v1.4119 Chirag Patel Added reviews for gene SCN10A from panel Genetic Epilepsy
Mendeliome v1.4118 Bryony Thompson Copied gene GPR88 from panel Dystonia and Chorea
Mendeliome v1.4118 GPR88 Bryony Thompson gene: GPR88 was added
gene: GPR88 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPR88 were set to 27123486
Phenotypes for gene: GPR88 were set to chorea, childhood-onset, with psychomotor retardation MONDO:0014839
Mendeliome v1.4117 S100A3 Zornitza Stark Marked gene: S100A3 as ready
Mendeliome v1.4117 S100A3 Zornitza Stark Gene: s100a3 has been classified as Red List (Low Evidence).
Mendeliome v1.4117 S100A3 Zornitza Stark gene: S100A3 was added
gene: S100A3 was added to Mendeliome. Sources: Literature
digenic tags were added to gene: S100A3.
Mode of inheritance for gene: S100A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: S100A3 were set to 40497957; 38099297; 31073086
Phenotypes for gene: S100A3 were set to Pulmonary fibrosis, MONDO:0002771, S100A3-related
Review for gene: S100A3 was set to RED
Added comment: PMID 31073086 reports 13 individuals from 2 unrelated families, with early‑onset (age 12-15) atypical familial pulmonary fibrosis caused by hypomorphic S100A3 missense variant in a digenic context with high impact S100A13 homozygous variant. Functional studies in patient‑derived fibroblasts, iPSC‑derived alveolar cells and rescue experiments demonstrate reduced S100A3 expression, impaired calcium signalling, mitochondrial dysfunction and cytokine dysregulation, supporting pathogenicity.

However, note variant c.229C>T (p.R77C) is present in homozygous state in 12 individuals in gnomAD v4, hence S100A3 variant may be solely responsible.
Sources: Literature
Mendeliome v1.4116 GSPT2 Morten Herlin reviewed gene: GSPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 41420488; Phenotypes: MONDO:0700092; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.4116 S100A13 Zornitza Stark changed review comment from: PMID 31073086 reports 13 individuals from 2 families with early‑onset atypical familial pulmonary fibrosis caused by homozygous loss‑of‑function truncating S100A13 variants in digenic combination with S100A3 homozygous missense variant; functional studies in patient fibroblasts and iPSC‑derived alveolar cells show reduced S100A13 expression, altered calcium signalling and mitochondrial dysfunction that are rescued by wild‑type S100A13.
Sources: Literature; to: PMID 31073086 reports 13 individuals from 2 families with early‑onset (age 12-15) atypical familial pulmonary fibrosis caused by homozygous loss‑of‑function truncating S100A13 variants in digenic combination with S100A3 homozygous missense variant; functional studies in patient fibroblasts and iPSC‑derived alveolar cells show reduced S100A13 expression, altered calcium signalling and mitochondrial dysfunction that are rescued by wild‑type S100A13.
Sources: Literature
Mendeliome v1.4116 S100A13 Zornitza Stark Marked gene: S100A13 as ready
Mendeliome v1.4116 S100A13 Zornitza Stark Gene: s100a13 has been classified as Red List (Low Evidence).
Mendeliome v1.4116 S100A13 Zornitza Stark gene: S100A13 was added
gene: S100A13 was added to Mendeliome. Sources: Literature
digenic tags were added to gene: S100A13.
Mode of inheritance for gene: S100A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: S100A13 were set to 40497957; 38099297; 31073086
Phenotypes for gene: S100A13 were set to Pulmonary fibrosis, MONDO:0002771, S100A13-related
Review for gene: S100A13 was set to RED
Added comment: PMID 31073086 reports 13 individuals from 2 families with early‑onset atypical familial pulmonary fibrosis caused by homozygous loss‑of‑function truncating S100A13 variants in digenic combination with S100A3 homozygous missense variant; functional studies in patient fibroblasts and iPSC‑derived alveolar cells show reduced S100A13 expression, altered calcium signalling and mitochondrial dysfunction that are rescued by wild‑type S100A13.
Sources: Literature
Mendeliome v1.4115 BOC Zornitza Stark Marked gene: BOC as ready
Mendeliome v1.4115 BOC Zornitza Stark Gene: boc has been classified as Red List (Low Evidence).
Mendeliome v1.4115 BOC Zornitza Stark Phenotypes for gene: BOC were changed from to Orofacial clefting, MONDO:0000358, BOC-related
Mendeliome v1.4114 BOC Zornitza Stark edited their review of gene: BOC: Changed phenotypes: Orofacial clefting, MONDO:0000358, BOC-related
Mendeliome v1.4114 OSR2 Sangavi Sivagnanasundram gene: OSR2 was added
gene: OSR2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OSR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OSR2 were set to 41424369; 21262216
Phenotypes for gene: OSR2 were set to MONDO:0005497
Review for gene: OSR2 was set to GREEN
Added comment: 41424369 reports six unrelated families (13 affected individuals) presenting with radioulnar synostosis, distal ulna hypoplasia, joint stiffness, ear deformities, scoliosis and short stature.

Variant: two nonsense, two missense at the same codon, and a 383‑kb deletion were reported. The variants segregate in an autosomal‑dominant pattern with incomplete penetrance and was identified de novo in one family

Functional assays (Western blot, immunofluorescence) demonstrate loss‑of‑function.

21262216 - Reports Osr2 knockout mice that recapitulate the human phenotype of joint fusion, supporting the loss-of-function mechanism of the disease.
Sources: Literature
Mendeliome v1.4113 BOC Zornitza Stark gene: BOC was added
gene: BOC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BOC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BOC were set to 40464334; 28677295
Review for gene: BOC was set to RED
Added comment: BOC encodes a cell‑surface co‑receptor for Sonic Hedgehog signaling. PMID 40464334 reports 4 unrelated families with heterozygous BOC variants causing non‑syndromic orofacial clefts (cleft palate and microform cleft lip); three variants are de novo and one segregates dominantly, and zebrafish and cell‑based assays confirm hypomorphic activity. PMID 28677295 and PMID 28915250 describe BOC missense variants in holoprosencephaly and Gorlin syndrome, respectively, but present them as modifier alleles without segregation or functional validation.

However, all reported variants have relatively high gnomAD frequencies, raising the possibility that these are susceptibility alleles.
Sources: Literature
Mendeliome v1.4112 AXDND1 Zornitza Stark Classified gene: AXDND1 as Green List (high evidence)
Mendeliome v1.4112 AXDND1 Zornitza Stark Gene: axdnd1 has been classified as Green List (High Evidence).
Mendeliome v1.4111 AXDND1 Zornitza Stark edited their review of gene: AXDND1: Added comment: PMID 38997255: Reports 3 individuals from 3 unrelated families with autosomal recessive loss‑of‑function or missense variants in AXDND1 presenting with non‑obstructive azoospermia/severe oligozoospermia. One family carries a homozygous stop‑gain (p.R313X) and two families carry heterozygous missense variants (p.Leu536Gln; p.Lys817Asn) with phenotypes ranging from Sertoli‑cell‑only syndrome to hypospermatogenesis. A mouse Ax​dnd1 knockout recapitulates male infertility, defective spermatogenesis and abnormal sperm tail ultrastructure, providing strong functional validation of gene loss‑of‑function as the disease mechanism.; Changed rating: GREEN; Changed publications: 40457935, 38997255
Mendeliome v1.4111 UNC13C Sangavi Sivagnanasundram gene: UNC13C was added
gene: UNC13C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UNC13C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC13C were set to 41399760
Phenotypes for gene: UNC13C were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: UNC13C was set to AMBER
Added comment: PMID 41399760 reports 11 individuals from 9 unrelated families with biallelic nonsense and missense UNC13C variants presenting with a severe neurodevelopmental disorder (global developmental delay, microcephaly, autism spectrum disorder, brain malformations, hypotonia). Inheritance is autosomal recessive. Drosophila knock‑in models examined ethanol sensitivity but did not reproduce neurodevelopmental phenotypes, offering limited functional support for pathogenicity.

Multiple different biallelic variants were reported - all were either absent or rare enough for AR gene in gnomAD v4.1 except for c.283C>T(p.Arg95Ter) which has a FAF of 0.4409%
Sources: Literature
Mendeliome v1.4110 SCN10A Chirag Patel reviewed gene: SCN10A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4110 Chirag Patel Added reviews for gene SEPT2 from panel Mendeliome
Mendeliome v1.4109 SEPT2 Chirag Patel Marked gene: SEPT2 as ready
Mendeliome v1.4109 SEPT2 Chirag Patel Gene: sept2 has been classified as Green List (High Evidence).
Mendeliome v1.4109 SEPT2 Chirag Patel Classified gene: SEPT2 as Green List (high evidence)
Mendeliome v1.4109 SEPT2 Chirag Patel Gene: sept2 has been classified as Green List (High Evidence).
Mendeliome v1.4108 SEPT2 Chirag Patel gene: SEPT2 was added
gene: SEPT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEPT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEPT2 were set to 41408595
Phenotypes for gene: SEPT2 were set to Neurodevelopmental disorder, MONDO:0700092, SEPTIN2-related
Review for gene: SEPT2 was set to GREEN
Added comment: 7 individuals from 6 families (5 unrelated) with heterozygous missense SEPTIN2 variants causing a neurodevelopmental disorder. Clinical features included developmental delay/intellectual disability (6/7), hearing loss (4/7), cleft palate (3/7), ptosis (3/7), septal heart defect (2/7), syndactyly (2/7), and ADHD (2/7).

Most variants were de novo (5 families) except 1 family where the variant was inherited from an affected mother. Functional assays demonstrated dominant‑negative disruption of Septin‑2 homodimerisation and axon initial segment formation. Expression of mutant Septin-2 constructs in neurons leads to the disappearance of canonical hallmarks of the axon initial segment.
Sources: Literature
Mendeliome v1.4107 PTPN13 Sangavi Sivagnanasundram reviewed gene: PTPN13: Rating: AMBER; Mode of pathogenicity: None; Publications: 41422331, 29093530; Phenotypes: bone marrow failure syndrome MONDO:0000159, PTPN13-related, Hirschsprung disease MONDO:0018309; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4107 PCBP1 Sarah Milton gene: PCBP1 was added
gene: PCBP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PCBP1 were set to 41415500
Phenotypes for gene: PCBP1 were set to Neurodevelopmental disorder, MONDO:0700092, PCBP1-related
Review for gene: PCBP1 was set to GREEN
Added comment: Below information taken from pre print paper.

PCBP1 encodes the poly(rC)-binding protein 1, an RNA‑binding protein involved in transcriptional and translational processes and splicing.

PMID 41415500 reports 13 unrelated individuals with heterozygous de‑novo truncating or missense variants in PCBP1 presenting with a neurodevelopmental disorder characterized by intellectual disability, autism spectrum disorder, hypotonia, and variable additional features (seizures 3/13, microcephaly 3/13, ophthalmologic features 6/13).

All variants absent from gnomAD v4 and LOF proposed mechanism of disease with a significant paucity of LOF variants in the gene in gnomAD.

Functional assays in primary mouse hippocampal neurons transfected with patient variants showed mixed results. RNA‑sequencing from three of the patients showed altered splicing of other genes thought secondary to variants in PCBP1.
Sources: Literature
Mendeliome v1.4106 NOS3 Zornitza Stark Phenotypes for gene: NOS3 were changed from Moyamoya disease, MONDO:0016820 to Moyamoya disease 8, MIM# 621469
Mendeliome v1.4105 MAEA Bryony Thompson Classified gene: MAEA as Green List (high evidence)
Mendeliome v1.4105 MAEA Bryony Thompson Gene: maea has been classified as Green List (High Evidence).
Mendeliome v1.4104 MAEA Bryony Thompson Publications for gene: MAEA were set to 40880485
Mendeliome v1.4103 MAEA Bryony Thompson reviewed gene: MAEA: Rating: GREEN; Mode of pathogenicity: None; Publications: 41420108, 40880485; Phenotypes: Neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4103 TENM4 Bryony Thompson Classified gene: TENM4 as Amber List (moderate evidence)
Mendeliome v1.4103 TENM4 Bryony Thompson Gene: tenm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4102 TENM4 Bryony Thompson gene: TENM4 was added
gene: TENM4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TENM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TENM4 were set to 41449293; 36689009; 26188006; 29249217; 34589676; 22915103
Phenotypes for gene: TENM4 were set to Neurodevelopmental disorder, MONDO:0700092; tremor, hereditary essential, 5 MONDO:0014756; first branchial cleft anomaly MONDO:0015376
Review for gene: TENM4 was set to AMBER
Added comment: TENM4 encodes a type II transmembrane teneurin involved in neuronal development and oligodendrocyte maturation.

Amber for essential tremor - 2 families with rare missense and supporting segregation evidence, plus mouse & zebrafish models. 2 other GDAs have limited evidence.
PMID 26188006 - 3 families reported with essential tremor with incomplete segregation. 2 of the variants (p.Ala1442Thr and p.Val1138Met) are more common than expected in gnomAD. p.Thr1367Asn is a rare missense and segregates with ET over 3 generations (2 unaffected carriers under the average age of onset). Functional assays demonstrate dominant‑negative effects in oligodendrocyte precursor cells and zebrafish axon‑guidance defects for all 3 variants.
 PMID 36689009 - rare heterozygous missense (p.P421L) segregating in 5 affected individuals with ET in a single family
 PMID 29249217 -  a case with hereditary tremor‑like syndrome with palatal tremor but no description of the TENM4 variant in the paper.
PMID 22915103 - myelination of small-diameter axons was dramatically reduced, and differentiation of oligodendrocytes, the myelin-forming cells in the CNS, was inhibited in null mouse model.

PMID 34589676 - 2 rare missense in 2 patients with first branchial cleft anomalies. No other evidence. Multiple missense in different genes in one of the patients. - limited evidence for gene-disease association

PMID 41449293 - rare splice variant identified in a single family (segregates in 6 individuals) with childhood‑onset intellectual disability with epilepsy. Splice‑site‑mediated exon 10 skipping leading to seizures in a mouse model, supporting a pathogenic role. - single family reported
Sources: Literature
Mendeliome v1.4101 WNT1 Zornitza Stark Mode of inheritance for gene: WNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4100 TNNT3 Zornitza Stark Phenotypes for gene: TNNT3 were changed from Arthrogryposis, distal, type 2B2, MIM# 618435 to Arthrogryposis, distal, type 2B2, MIM# 618435; Nemaline myopathy MONDO:0018958
Mendeliome v1.4099 TNNT3 Zornitza Stark Mode of inheritance for gene: TNNT3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4098 TNNT3 Zornitza Stark edited their review of gene: TNNT3: Added comment: Three individuals from two unrelated families with bi-allelic variants and nemaline myopathy.; Changed publications: 12865991, 19142688, 21402185, 25337069, 17194691, 33977145, 29266598, 23775847; Changed phenotypes: Arthrogryposis, distal, type 2B2, MIM# 618435, Nemaline myopathy MONDO:0018958; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4098 NOD2 Zornitza Stark Phenotypes for gene: NOD2 were changed from Blau syndrome, MIM# 186580 to Blau syndrome, MIM# 186580; {Inflammatory bowel disease 1, Crohn disease} 266600; {Yao syndrome} 617321
Mendeliome v1.4097 NOD2 Zornitza Stark Publications for gene: NOD2 were set to 15459013
Mendeliome v1.4096 NOD2 Zornitza Stark Mode of inheritance for gene: NOD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4095 NOD2 Zornitza Stark edited their review of gene: NOD2: Added comment: PMID 33692434 reports 92 unrelated families with biallelic loss‑of‑function NOD2 variants causing early‑onset Crohn’s disease.
Yao syndrome (YAOS) is an autoinflammatory disease characterized by periodic fever, dermatitis, arthritis, and swelling of the distal extremities, as well as gastrointestinal and sicca-like symptoms. PMID 39372397 describes 152 adult‑onset Yao syndrome patients, many carrying the cis‑regulatory IVS8+158 variant that shows functional gain‑of‑function.; Changed publications: 15459013, 11385576, 17804789, 32463623, 33692434, 39372397; Changed phenotypes: Blau syndrome, MIM# 186580, {Inflammatory bowel disease 1, Crohn disease} 266600, {Yao syndrome} 617321; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4095 NCSTN Zornitza Stark Phenotypes for gene: NCSTN were changed from to Acne inversa, familial, 1 MIM#142690
Mendeliome v1.4094 NCSTN Zornitza Stark Publications for gene: NCSTN were set to
Mendeliome v1.4093 NCSTN Zornitza Stark Mode of inheritance for gene: NCSTN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4092 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from Ellis-van Creveld syndrome (MIM#225500) to Ellis-van Creveld syndrome (MIM#225500); Weyers acrofacial dysostosis, MIM# 193530
Mendeliome v1.4091 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4090 EVC2 Zornitza Stark edited their review of gene: EVC2: Added comment: Variants associated with Weyers acrofacial dysostosis cluster in exon 22.; Changed phenotypes: Ellis-van Creveld syndrome (MIM#225500), Weyers acrofacial dysostosis, MIM# 193530; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4090 B3GNT4 Sarah Milton gene: B3GNT4 was added
gene: B3GNT4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: B3GNT4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GNT4 were set to 41444428
Phenotypes for gene: B3GNT4 were set to Hereditary neurological disease, MONDO:0100545, B3GNT4-related
Review for gene: B3GNT4 was set to RED
Added comment: PMID 41444428 reports 1 individual from 1 family with autosomal recessive homozygous missense variant c.478G>T (p.G160W) presenting with late‑onset progressive brain atrophy and muscular dystrophy. The patient had normal development until age 8, then progressive motor decline, spastic paresis, severe muscle wasting, elevated CK, loss of language, and died at 47 years of age from respiratory failure. A knock‑in mouse model reproduces the muscle but not CNS aspects of phenotype.
Sources: Literature
Mendeliome v1.4089 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851 to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851; Retinitis pigmentosa, MONDO:0019200, RNU4-2 related
Mendeliome v1.4088 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38991538; 40297424
Mendeliome v1.4087 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Added comment: PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT; Changed publications: 38991538, 40297424, 39830270; Changed phenotypes: Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851, Retinitis pigmentosa, MONDO:0019200, RNU4-2 related
Mendeliome v1.4087 AP1M2 Zornitza Stark Marked gene: AP1M2 as ready
Mendeliome v1.4087 AP1M2 Zornitza Stark Gene: ap1m2 has been classified as Red List (Low Evidence).
Mendeliome v1.4087 AP1M2 Zornitza Stark gene: AP1M2 was added
gene: AP1M2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AP1M2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1M2 were set to 41451456
Phenotypes for gene: AP1M2 were set to Inborn error of immunity, MONDO:0003778
Review for gene: AP1M2 was set to RED
Added comment: PMID 41451456 reports a single individual with biallelic splice‑site loss‑of‑function variant presenting with early‑onset autoinflammatory disease with severe colitis, failure‑to‑thrive, and perianal fistula. Functional studies demonstrate exon 10 skipping, loss of μ‑subunit interaction with TGN38, NF‑κB hyperactivation, and colitis in Ap1m2‑deficient mice that is rescued by TNFR1 knockout.
Sources: Literature
Mendeliome v1.4086 NDUFA3 Zornitza Stark Publications for gene: NDUFA3 were set to 41038977; 39661167
Mendeliome v1.4085 NDUFA3 Zornitza Stark Classified gene: NDUFA3 as Green List (high evidence)
Mendeliome v1.4085 NDUFA3 Zornitza Stark Gene: ndufa3 has been classified as Green List (High Evidence).
Mendeliome v1.4084 NDUFA3 Zornitza Stark edited their review of gene: NDUFA3: Added comment: Third unrelated family reported in PMID 41404351, intronic variants with abnormal splicing demonstrated.; Changed rating: GREEN; Changed publications: 41038977, 39661167, 41404351
Mendeliome v1.4084 G6PC Zornitza Stark Marked gene: G6PC as ready
Mendeliome v1.4084 G6PC Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is G6PC1.
Mendeliome v1.4084 G6PC Zornitza Stark Gene: g6pc has been classified as Green List (High Evidence).
Mendeliome v1.4084 G6PC Zornitza Stark Tag new gene name tag was added to gene: G6PC.
Mendeliome v1.4084 MIR17HG Zornitza Stark Classified gene: MIR17HG as Amber List (moderate evidence)
Mendeliome v1.4084 MIR17HG Zornitza Stark Gene: mir17hg has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4083 MIR17HG Zornitza Stark changed review comment from: 4 unrelated cases reported - 3 with gene deletions, 1 with SNV
Sources: Expert list; to: 4 unrelated cases reported - 3 with gene deletions, 1 with SNV. The deletions include portion of GPC5 as well.
Sources: Expert list
Mendeliome v1.4083 MIR17HG Zornitza Stark edited their review of gene: MIR17HG: Changed rating: AMBER
Mendeliome v1.4083 MIR17HG Zornitza Stark Tag SV/CNV tag was added to gene: MIR17HG.
Mendeliome v1.4083 MIR17HG Zornitza Stark edited their review of gene: MIR17HG: Added comment: Multiple mouse models.; Changed publications: 25391829, 21892160, 29636449
Mendeliome v1.4083 MIR140 Zornitza Stark Classified gene: MIR140 as Amber List (moderate evidence)
Mendeliome v1.4083 MIR140 Zornitza Stark Gene: mir140 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4082 MIR140 Zornitza Stark edited their review of gene: MIR140: Added comment: LIMITED by ClinGen.; Changed rating: AMBER; Changed phenotypes: Spondyloepiphyseal dysplasia, Nishimura type, MIM# 618618
Mendeliome v1.4082 BAIAP2 Zornitza Stark Phenotypes for gene: BAIAP2 were changed from BAIAP2-related complex neurodevelopmental disorder MONDO:0100038 to Developmental and epileptic encephalopathy 120, MIM# 621468
Mendeliome v1.4081 BAIAP2 Zornitza Stark reviewed gene: BAIAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 120, MIM# 621468; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4081 MYO9B Zornitza Stark Publications for gene: MYO9B were set to 16720215; 16423886; 16282976
Mendeliome v1.4080 MYO9B Zornitza Stark reviewed gene: MYO9B: Rating: AMBER; Mode of pathogenicity: None; Publications: 40382695; Phenotypes: Charcot-Marie-Tooth disease type 2 (MONDO:0018993), MYO9B-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4080 JUP Zornitza Stark Mode of inheritance for gene: JUP was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4079 JUP Zornitza Stark changed review comment from: Association between mono-allelic variants and ARVC: DEFINITIVE by ClinGen.

Association between bi-allelic variants and Naxos: more than 5 unrelated families reported.; to: Association between bi-allelic variants and ARVC/Naxos: DEFINITIVE by ClinGen.
Mendeliome v1.4079 JUP Zornitza Stark edited their review of gene: JUP: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4079 SCAMP5 Zornitza Stark Phenotypes for gene: SCAMP5 were changed from Intellectual disability; seizures; autism to Neurodevelopmental disorder, MONDO:0700092, SCAMP5-related
Mendeliome v1.4078 SCAMP5 Zornitza Stark edited their review of gene: SCAMP5: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SCAMP5-related
Mendeliome v1.4078 COPB1 Zornitza Stark Classified gene: COPB1 as Green List (high evidence)
Mendeliome v1.4078 COPB1 Zornitza Stark Gene: copb1 has been classified as Green List (High Evidence).
Mendeliome v1.4077 COPB1 Zornitza Stark edited their review of gene: COPB1: Added comment: PMID 40396222 adds two siblings from a consanguineous Pakistani family with a homozygous missense variant c.2693G>T (p.Arg898Leu) and consistent phenotype. Combined evidence comprises eight patients from three unrelated families, loss‑of‑function mechanism, and functional validation including splice disruption, Xenopus CRISPR modelling, protein stability/Golgi localisation assays, and in silico structural modeling.; Changed rating: GREEN; Changed publications: 40396222, 33632302; Changed phenotypes: Baralle-Macken syndrome, MIM# 619255
Mendeliome v1.4077 CNP Zornitza Stark edited their review of gene: CNP: Changed phenotypes: Leukodystrophy, hypomyelinating, 20, MIM# 619071
Mendeliome v1.4077 CNP Zornitza Stark Publications for gene: CNP were set to 32128616; 12590258
Mendeliome v1.4076 CNP Zornitza Stark Classified gene: CNP as Green List (high evidence)
Mendeliome v1.4076 CNP Zornitza Stark Gene: cnp has been classified as Green List (High Evidence).
Mendeliome v1.4075 CNP Zornitza Stark edited their review of gene: CNP: Added comment: PMID 40396300 adds two affected siblings from an independent consanguineous family with a homozygous nonsense CNP variant (p.Glu99*) resulting in hypomyelinating leukodystrophy type 20.; Changed rating: GREEN; Changed publications: 40396300, 32128616; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4075 SPAG17 Zornitza Stark Publications for gene: SPAG17 were set to 28548327
Mendeliome v1.4074 SPAG17 Zornitza Stark Classified gene: SPAG17 as Green List (high evidence)
Mendeliome v1.4074 SPAG17 Zornitza Stark Gene: spag17 has been classified as Green List (High Evidence).
Mendeliome v1.4073 SPAG17 Zornitza Stark edited their review of gene: SPAG17: Added comment: Recent studies (PMIDs 28548327, 39686771, 40330001 and supporting mouse data in PMID 29690537) expand SPAG17‑associated male infertility to four unrelated families (seven affected individuals) with biallelic loss‑of‑function variants causing severe asthenozoospermia, multiple morphological abnormalities of the flagella (MMAF) or oligoasthenoteratozoospermia. Detailed semen analyses, sperm ultrastructure, immunofluorescence, Western blot, qPCR and TEM demonstrate loss of SPAG17 protein and axonemal defects, while a Spag17 knockout mouse recapitulates the infertility phenotype.; Changed rating: GREEN; Changed publications: 40330001, 39686771, 28548327
Mendeliome v1.4073 C1orf146 Zornitza Stark Marked gene: C1orf146 as ready
Mendeliome v1.4073 C1orf146 Zornitza Stark Gene: c1orf146 has been classified as Red List (Low Evidence).
Mendeliome v1.4073 C1orf146 Zornitza Stark gene: C1orf146 was added
gene: C1orf146 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C1orf146 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1orf146 were set to 40374915; 37270785
Phenotypes for gene: C1orf146 were set to Infertility disorder, MONDO:0005047, C1orf146-related
Review for gene: C1orf146 was set to RED
Added comment: PMID 37270785 reports a 36‑year‑old woman with a homozygous splice‑site loss‑of‑function SPO16 variant (c.160+8A>G) presenting with premature ovarian insufficiency; minigene splicing assays demonstrated exon 3 skipping. PMID 40374915 describes a male from a separate unrelated family carrying a homozygous frameshift SPO16 variant (c.266del) who has non‑obstructive azoospermia with meiotic arrest; no functional studies were performed.
Sources: Literature
Mendeliome v1.4072 SKIV2L Zornitza Stark commented on gene: SKIV2L: New HGNC approved name is SKIC2
Mendeliome v1.4072 SKIV2L Zornitza Stark Tag new gene name tag was added to gene: SKIV2L.
Mendeliome v1.4072 HBD Zornitza Stark Marked gene: HBD as ready
Mendeliome v1.4072 HBD Zornitza Stark Gene: hbd has been classified as Green List (High Evidence).
Mendeliome v1.4072 Zornitza Stark Copied gene HBD from panel Red cell disorders
Mendeliome v1.4072 HBD Zornitza Stark gene: HBD was added
gene: HBD was added to Mendeliome. Sources: Expert Review Green,Yorkshire and North East GLH,NHS GMS,Wessex and West Midlands GLH,North West GLH,London South GLH
Mode of inheritance for gene: HBD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HBD were set to 27630894; 25490067
Phenotypes for gene: HBD were set to Thalassaemia, delta-; Thalassaemia due to Hb Lepore
Mendeliome v1.4071 PFAS Zornitza Stark Marked gene: PFAS as ready
Mendeliome v1.4071 PFAS Zornitza Stark Gene: pfas has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4071 PFAS Zornitza Stark Classified gene: PFAS as Amber List (moderate evidence)
Mendeliome v1.4071 PFAS Zornitza Stark Gene: pfas has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4070 PFAS Zornitza Stark gene: PFAS was added
gene: PFAS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PFAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PFAS were set to 40421664
Phenotypes for gene: PFAS were set to Inborn error of metabolism, MONDO:0019052, PFAS-related
Review for gene: PFAS was set to AMBER
Added comment: PMID 40421664 reports 2 individuals from 2 unrelated families with biallelic missense variants presenting with prematurity, short stature, seizures, and mild neurodevelopmental impairment. Functional studies in patient fibroblasts show ~30% PFAS protein, ~16% enzyme activity, impaired purinosome formation, and rescue of purinosome formation and FGAR levels by wild‑type PFAS, supporting pathogenicity.
Sources: Literature
Mendeliome v1.4069 MAEL Zornitza Stark Marked gene: MAEL as ready
Mendeliome v1.4069 MAEL Zornitza Stark Gene: mael has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4069 MAEL Zornitza Stark Classified gene: MAEL as Amber List (moderate evidence)
Mendeliome v1.4069 MAEL Zornitza Stark Gene: mael has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4068 MAEL Zornitza Stark gene: MAEL was added
gene: MAEL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAEL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAEL were set to 40442410; 39122675
Phenotypes for gene: MAEL were set to Spermatogenic failure, MONDO:0004983, MAEL-related
Review for gene: MAEL was set to AMBER
Added comment: PMID 39122675 reports 1 individual and PMID 40442410 reports a second individual, together 2 unrelated families with autosomal recessive loss‑of‑function MAEL variants causing non‑obstructive azoospermia with meiotic arrest (male infertility). Functional evidence includes a minigene splicing assay and IHC loss of MAEL protein, as well as protein structural modelling, evolutionary conservation analysis, and a mouse knockout model that recapitulates spermatogenic failure.
Sources: Literature
Mendeliome v1.4067 LY9 Zornitza Stark Marked gene: LY9 as ready
Mendeliome v1.4067 LY9 Zornitza Stark Gene: ly9 has been classified as Green List (High Evidence).
Mendeliome v1.4067 LY9 Zornitza Stark Classified gene: LY9 as Green List (high evidence)
Mendeliome v1.4067 LY9 Zornitza Stark Gene: ly9 has been classified as Green List (High Evidence).
Mendeliome v1.4066 LY9 Zornitza Stark gene: LY9 was added
gene: LY9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LY9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LY9 were set to 40446017
Phenotypes for gene: LY9 were set to Inborn error of immunity, MONDO:0003778, LY9-related
Review for gene: LY9 was set to GREEN
Added comment: PMID 40446017 reports three individuals from three unrelated families with biallelic loss-of-function LY9 frameshift variants presenting with active tuberculosis (infant pulmonary TB, adult pulmonary TB, mediastinal tuberculous lymphadenitis). Detailed clinical phenotyping, segregation data, and rescue experiments demonstrate LY9 deficiency as the genetic cause of TB susceptibility.
Sources: Literature
Mendeliome v1.4065 FOXK2 Zornitza Stark Marked gene: FOXK2 as ready
Mendeliome v1.4065 FOXK2 Zornitza Stark Gene: foxk2 has been classified as Red List (Low Evidence).
Mendeliome v1.4065 FOXK2 Zornitza Stark gene: FOXK2 was added
gene: FOXK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXK2 were set to 40410591
Phenotypes for gene: FOXK2 were set to Myopathy, MONDO:0005336, FOXK2-related
Review for gene: FOXK2 was set to RED
Added comment: PMID 40410591 reports five affected individuals from one family with isolated congenital ptosis and additional affected individuals from four families with congenital myopathy and ptosis, all carrying heterozygous missense variants in FOXK2 inherited in an autosomal dominant manner; functional assays in zebrafish, muscle‑specific mouse knockout, and FOXK2‑KO C2C12 cells demonstrate reduced protein levels, impaired myogenic differentiation and mitochondrial dysfunction that are rescued by wild‑type FOXK2. However, all the variants are present in gnomAD, including one in over 2,000 individuals, hence Red rating.
Sources: Literature
Mendeliome v1.4064 DUSP1 Zornitza Stark Marked gene: DUSP1 as ready
Mendeliome v1.4064 DUSP1 Zornitza Stark Gene: dusp1 has been classified as Red List (Low Evidence).
Mendeliome v1.4064 DUSP1 Zornitza Stark gene: DUSP1 was added
gene: DUSP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DUSP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DUSP1 were set to 40359362
Phenotypes for gene: DUSP1 were set to Hereditary palmoplantar keratoderma, MONDO:0019272, DUSP1-related
Review for gene: DUSP1 was set to RED
Added comment: PMID 40359362 reports four individuals from two unrelated families with heterozygous and homozygous missense variants in DUSP1 presenting with semidominant palmoplantar keratoderma, focal hyperkeratosis, and, in homozygotes, severe PPK with hearing loss. Functional assays in primary keratinocytes and 3‑D skin equivalents demonstrate reduced DUSP1 protein, increased ERK1/2 phosphorylation, and rescue by ERK1/2 inhibition. The inheritance is postulated to be semidominant (monoallelic and biallelic) with dose‑dependent severity -- one family has two heterozygous individuals (insufficient segregation) and second family has a more severely affected homozygous individual and affected parent.
Sources: Literature
Mendeliome v1.4063 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38991538
Mendeliome v1.4062 RNU4-2 Zornitza Stark Mode of inheritance for gene: RNU4-2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4061 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Added comment: PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.; Changed publications: 38991538, 40297424; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4061 ITGB3 Zornitza Stark Phenotypes for gene: ITGB3 were changed from Bleeding disorder, platelet-type, 24, MIM#619271; MONDO:0008552 to Bleeding disorder, platelet-type, 24, MIM#619271; MONDO:0008552; Glanzmann thrombasthenia 2, MIM# 619267
Mendeliome v1.4060 ITGB3 Zornitza Stark Mode of inheritance for gene: ITGB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4059 ITGB3 Zornitza Stark edited their review of gene: ITGB3: Added comment: Multiple families reported with biallelic variants and Glanzmann thrombasthenia.; Changed publications: 18065693, 19336737, 20081061, 23253071, 20020534; Changed phenotypes: Bleeding disorder, platelet-type, 24, MIM#619271, MONDO:0008552, Glanzmann thrombasthenia 2, MIM# 619267; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4059 ATP9A Zornitza Stark Publications for gene: ATP9A were set to 34379057; 34764295
Mendeliome v1.4058 ATP9A Zornitza Stark Mode of inheritance for gene: ATP9A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4057 ATP9A Zornitza Stark edited their review of gene: ATP9A: Added comment: PMIDs 34379057, 34764295, 36604604 and 40226306 report 12 unrelated families with ATP9A variants. Six families carry biallelic loss‑of‑function variants causing an autosomal recessive neurodevelopmental disorder with post‑natal microcephaly, failure‑to‑thrive and behavioural abnormalities; five families carry de novo heterozygous missense variants causing autosomal dominant nonsyndromic intellectual disability with seizures and autism‑like features. Multiple functional studies in patient cells, mouse knock‑out models and rescue assays provide strong loss‑of‑function evidence.; Changed publications: 40226306, 36604604, 34764295, 34379057; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4057 LATS1 Sangavi Sivagnanasundram gene: LATS1 was added
gene: LATS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LATS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LATS1 were set to 35986120
Phenotypes for gene: LATS1 were set to cerebral cavernous malformations MONDO:0031037
Review for gene: LATS1 was set to RED
Added comment: LATS1 encodes a serine‑threonine kinase in the Hippo signaling pathway that regulates YAP activity.
One reported Chinese family with missense variant (c.821C>T, p.Thr274Ile) in LATS1 and a phenotype consistent with CCM on imaging. The variant appeared to segregate in the family in affected individuals however there are multiple individuals that weren't assessed.
Sources: Literature
Mendeliome v1.4056 YME1L1 Zornitza Stark Phenotypes for gene: YME1L1 were changed from Optic atrophy 11, MIM#617302 to Optic atrophy 11, MIM#617302; Mitochondrial disease, MONDO:0044970, YME1L1-related
Mendeliome v1.4055 YME1L1 Zornitza Stark Publications for gene: YME1L1 were set to 30544562; 27495975
Mendeliome v1.4054 YME1L1 Zornitza Stark edited their review of gene: YME1L1: Added comment: PMID 40255048: Reports 2 individuals from a single family with a homozygous missense variant NM_014263.4:c.1999C>G (p.Leu667Val) presenting with childhood‑onset sensorineural hearing loss, developmental delay, basal ganglia MRI hyperintensity, and marked 3‑methylglutaconic and 3‑methylglutaric aciduria. Patient‑derived fibroblasts display abnormal OPA1 and PRELID1 processing, increased mitochondrial fragmentation, reduced citrate synthase and α‑ketoglutarate dehydrogenase activities, and diminished oxygen consumption, supporting a loss‑of‑function mechanism.; Changed publications: 30544562, 27495975, 40255048; Changed phenotypes: Optic atrophy 11, MIM#617302, Mitochondrial disease, MONDO:0044970, YME1L1-related
Mendeliome v1.4054 PACRG Zornitza Stark Phenotypes for gene: PACRG were changed from to Spermatogenic failure, MONDO:0004983, PACRG-related
Mendeliome v1.4053 PACRG Zornitza Stark Publications for gene: PACRG were set to 31116684; 31182890; 14737177; 27193298
Mendeliome v1.4052 PACRG Zornitza Stark Mode of inheritance for gene: PACRG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4051 PACRG Zornitza Stark edited their review of gene: PACRG: Added comment: PMID 34089056 and PMID 40298292 report 2 individuals from 2 families with biallelic loss-of-function variants presenting with severe sperm head defects and impaired motility (DFS‑MMAF), causing male infertility. Both studies provide detailed clinical phenotyping but lack segregation analysis and functional validation. Also, both report the same variant so can't be certain the individuals are unrelated.; Changed publications: 40298292, 34089056; Changed phenotypes: Spermatogenic failure, MONDO:0004983, PACRG-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4051 SCYL2 Zornitza Stark Classified gene: SCYL2 as Green List (high evidence)
Mendeliome v1.4051 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Green List (High Evidence).
Mendeliome v1.4050 SCYL2 Zornitza Stark edited their review of gene: SCYL2: Added comment: PMID 31960134, 39169672, 40243816, and 36344539 collectively report seven unrelated families with biallelic SCYL2 variants. Five families present a severe syndromic arthrogryposis multiplex congenita (Zain syndrome/AMC4) featuring arthrogryposis, microcephaly, corpus callosum agenesis, optic atrophy, epilepsy and early lethality. Two families display a milder neurodevelopmental disorder with speech delay, autism spectrum disorder, intellectual disability and dysmorphic features but no arthrogryposis. Mouse knockout models and patient‑cell Western blot demonstrate loss‑of‑function, supporting pathogenicity.; Changed rating: GREEN; Changed publications: 40243816, 39169672, 31960134; Changed phenotypes: Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum, MIM# 618766
Mendeliome v1.4050 PPP5C Zornitza Stark Publications for gene: PPP5C were set to 35361529; 25363768; 33057194
Mendeliome v1.4049 PPP5C Zornitza Stark reviewed gene: PPP5C: Rating: AMBER; Mode of pathogenicity: None; Publications: 40172746; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPP5C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4049 PIGW Zornitza Stark Classified gene: PIGW as Green List (high evidence)
Mendeliome v1.4049 PIGW Zornitza Stark Gene: pigw has been classified as Green List (High Evidence).
Mendeliome v1.4048 PIGW Zornitza Stark edited their review of gene: PIGW: Added comment: PMIDs 40180615; 39924787; 39766333; 38055078: additional cases not included in ClinGen assessment, upgrade to Green.; Changed rating: GREEN; Changed publications: 24367057, 27626616, 30813920, 32198969, 40180615, 39924787, 39766333, 38055078
Mendeliome v1.4048 ESRP2 Zornitza Stark Phenotypes for gene: ESRP2 were changed from Orofacial cleft MONDO:0000358 to Orofacial cleft MONDO:0000358, ESRP2-related
Mendeliome v1.4047 ESRP2 Zornitza Stark Publications for gene: ESRP2 were set to 29805042
Mendeliome v1.4046 ESRP2 Zornitza Stark Classified gene: ESRP2 as Green List (high evidence)
Mendeliome v1.4046 ESRP2 Zornitza Stark Gene: esrp2 has been classified as Green List (High Evidence).
Mendeliome v1.4045 ESRP2 Zornitza Stark edited their review of gene: ESRP2: Added comment: Further functional work on some of the variants in PMID 39179789.; Changed rating: GREEN; Changed publications: 29805042, 39179789
Mendeliome v1.4045 RPS6KC1 Zornitza Stark Phenotypes for gene: RPS6KC1 were changed from Complex neurodevelopmental disorder, MONDO:0100038, RPS6KC1-related to Neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter, MIM# 621460
Mendeliome v1.4044 RPS6KC1 Zornitza Stark reviewed gene: RPS6KC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter, MIM# 621460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4044 GCH1 Bryony Thompson Mode of inheritance for gene: GCH1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4043 GCH1 Bryony Thompson Phenotypes for gene: GCH1 were changed from Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Hereditary spastic paraplegia MONDO:0019064, GCH1-related to GTP cyclohydrolase I deficiency MONDO:0100184
Mendeliome v1.4042 FAM83G Bryony Thompson Publications for gene: FAM83G were set to 29138053
Mendeliome v1.4041 FAM83G Bryony Thompson Classified gene: FAM83G as Green List (high evidence)
Mendeliome v1.4041 FAM83G Bryony Thompson Gene: fam83g has been classified as Green List (High Evidence).
Mendeliome v1.4040 FAM83G Bryony Thompson reviewed gene: FAM83G: Rating: GREEN; Mode of pathogenicity: None; Publications: 41384122, 39449644, 39043225, 29138053; Phenotypes: Hereditary palmoplantar keratoderma, MONDO:0019272, FAM83G-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4040 EGFLAM Bryony Thompson Marked gene: EGFLAM as ready
Mendeliome v1.4040 EGFLAM Bryony Thompson Gene: egflam has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4040 EGFLAM Bryony Thompson Classified gene: EGFLAM as Amber List (moderate evidence)
Mendeliome v1.4040 EGFLAM Bryony Thompson Gene: egflam has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4039 EGFLAM Bryony Thompson gene: EGFLAM was added
gene: EGFLAM was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EGFLAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EGFLAM were set to 41343198; 18641643
Phenotypes for gene: EGFLAM were set to Congenital stationary night blindness MONDO:0016293, EGFLAM-related
Review for gene: EGFLAM was set to AMBER
Added comment: PMID 41343198 reports two individuals from two unrelated Moroccan families with autosomal recessive loss-of-function truncating EGFLAM variants presenting with complete congenital stationary night blindness (cCSNB), characterised by childhood-onset night blindness, high myopia, reduced visual acuity, and an electronegative Schubert-Bornschein ERG pattern. The homozygous frameshift (p.Val522Glufs*18) and nonsense (p.Arg599*) variants cosegregated with disease.
PMID 18641643 Pikachurin null-mutant mice showed improper apposition of the bipolar cell dendritic tips to the photoreceptor ribbon synapses, resulting in alterations in synaptic signal transmission and visual function.
Sources: Literature
Mendeliome v1.4038 CDK4 Zornitza Stark Mode of inheritance for gene: CDK4 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4037 CDK4 Zornitza Stark Classified gene: CDK4 as Green List (high evidence)
Mendeliome v1.4037 CDK4 Zornitza Stark Gene: cdk4 has been classified as Green List (High Evidence).
Mendeliome v1.4036 Zornitza Stark Added reviews for gene CDK4 from panel Melanoma
Mendeliome v1.4035 CDK4 Zornitza Stark Phenotypes for gene: CDK4 were changed from {Melanoma, cutaneous malignant, 3} MIM#609048 to Neurodevelopmental disorder, MONDO:0700092; {Melanoma, cutaneous malignant, 3} MIM#609048
Mendeliome v1.4034 CDK4 Zornitza Stark Publications for gene: CDK4 were set to
Mendeliome v1.4033 CDK4 Zornitza Stark Mode of inheritance for gene: CDK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4032 CDK4 Zornitza Stark Classified gene: CDK4 as Amber List (moderate evidence)
Mendeliome v1.4032 CDK4 Zornitza Stark Gene: cdk4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4031 CDK4 Zornitza Stark reviewed gene: CDK4: Rating: AMBER; Mode of pathogenicity: None; Publications: 40210435; Phenotypes: Neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4031 MAU2 Zornitza Stark Marked gene: MAU2 as ready
Mendeliome v1.4031 MAU2 Zornitza Stark Gene: mau2 has been classified as Green List (High Evidence).
Mendeliome v1.4031 MAU2 Lucy Spencer Classified gene: MAU2 as Green List (high evidence)
Mendeliome v1.4031 MAU2 Lucy Spencer Gene: mau2 has been classified as Green List (High Evidence).
Mendeliome v1.4030 MAU2 Lucy Spencer gene: MAU2 was added
gene: MAU2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAU2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAU2 were set to 41332805; 37962004; 32433956
Phenotypes for gene: MAU2 were set to Cornelia de Lange syndrome MONDO:0016033, MAU2-related
Review for gene: MAU2 was set to GREEN
Added comment: PMID 41332805 report a total of 18 individuals from 15 unrelated families with heterozygous MAU2 variants causing Cornelia de Lange syndrome (1 of these patients was previously reported in PMID: 32433956). The main phenotypes in this cohort were short stature, microcephaly and ID, around half also had a mix of the characteristic CDLS facial features like synophrys, long smooth philtrum, thick eyebrows, thin upper lip vermilion and anteverted nares.

Variants include loss‑of‑function (nonsense, frameshift, splice‑affecting) that cause haploinsufficiency, and missense/in‑frame deletions some of which were shown to disrupt NIPBL‑MAU2 interaction. Most were de novo but several were transmitted from affected parents, and for 5 cases inheritance was unknown. All but one of the missense/inframe deletion variants is absent from gnomad v4, p.Cys50Ser is present with 6 heterozygotes and may not be pathogenic.

PMID: 37962004 has one additional patient with atypical Cornelia de Lange syndrome who has a de novo missense variant, absent from gnomad.
Sources: Literature
Mendeliome v1.4029 SMC1B Zornitza Stark Marked gene: SMC1B as ready
Mendeliome v1.4029 SMC1B Zornitza Stark Gene: smc1b has been classified as Red List (Low Evidence).
Mendeliome v1.4029 SMC1B Zornitza Stark gene: SMC1B was added
gene: SMC1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMC1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMC1B were set to 40180776; 27603904
Phenotypes for gene: SMC1B were set to Infertility disorder, MONDO:0005047, SMC1B-related
Review for gene: SMC1B was set to RED
Added comment: [PMID 27603904] reports 2 individuals from 2 families with heterozygous missense SMC1B variants (p.I221T, p.Q1177L) presenting with primary ovarian insufficiency. [PMID 40180776] reports 1 individual from 1 family with a heterozygous missense p.C619F variant causing severe necrozoospermia; the variant segregates from a carrier mother and functional assays show reduced SMC1B protein, indicating a loss‑of‑function mechanism. All three variants are present in the population, p.Q1177L at an implausibly high frequency.
Sources: Literature
Mendeliome v1.4028 MDN1 Zornitza Stark Marked gene: MDN1 as ready
Mendeliome v1.4028 MDN1 Zornitza Stark Gene: mdn1 has been classified as Red List (Low Evidence).
Mendeliome v1.4028 MDN1 Zornitza Stark gene: MDN1 was added
gene: MDN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MDN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDN1 were set to 40217384
Phenotypes for gene: MDN1 were set to Genetic epilepsy, MONDO:0100575, MDN1-related
Review for gene: MDN1 was set to RED
Added comment: PMID 40217384 reports 5 individuals from 5 unrelated families with biallelic missense or splice-site variants in MDN1 presenting with childhood-onset epilepsy (febrile seizures, febrile seizures plus, and focal epilepsy secondary to brain injury). Variants are rare in gnomAD with no homs. No experimental functional validation was performed and assertions of pathogenicity rely on in-silico assessment, hence RED rating.
Sources: Literature
Mendeliome v1.4027 PRDM15 Lucy Spencer Phenotypes for gene: PRDM15 were changed from Steroid resistant nephrotic syndrome; Holoprosencephaly to Multiple congenital anomalies MONDO:0019042, PRDM15-related
Mendeliome v1.4026 LMAN2L Lucy Spencer Phenotypes for gene: LMAN2L were changed from Mental retardation, autosomal recessive, 52 OMIM #616887; Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863 to Intellectual developmental disorder, autosomal dominant 69 MIM#617863; Intellectual developmental disorder, autosomal recessive 52 MIM#616887
Mendeliome v1.4025 LIPT1 Lucy Spencer Phenotypes for gene: LIPT1 were changed from Lipoyltransferase 1 deficiency, MIM#616299; Leigh-like presentation to Lipoyltransferase 1 deficiency, MIM#616299
Mendeliome v1.4024 LCAT Lucy Spencer Phenotypes for gene: LCAT were changed from Lecithin:Cholesterol Acyltransferase Deficiency, MIM# 245900; Fish-Eye disease, MIM# 136120 to Norum disease MIM#245900; Fish-Eye disease, MIM# 136120
Mendeliome v1.4023 LAMC2 Lucy Spencer Phenotypes for gene: LAMC2 were changed from Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650 to Epidermolysis bullosa, junctional 3A, intermediate MIM#619785; Epidermolysis bullosa, junctional 3B, severe MIM#619786
Mendeliome v1.4022 LAMB3 Lucy Spencer Phenotypes for gene: LAMB3 were changed from Amelogenesis imperfecta, type IA, MIM# 104530; Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650 to Amelogenesis imperfecta, type IA, MIM# 104530; Epidermolysis bullosa, junctional 1A, intermediate MIM#226650; Epidermolysis bullosa, junctional 1B, severe MIM#226700
Mendeliome v1.4021 LAMA2 Lucy Spencer Phenotypes for gene: LAMA2 were changed from Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138 to LAMA2-related muscular dystrophy MONDO:0100228; Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138
Mendeliome v1.4020 LAMA2 Lucy Spencer reviewed gene: LAMA2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: LAMA2-related muscular dystrophy MONDO:0100228; Mode of inheritance: None
Mendeliome v1.4020 KMT5B Lucy Spencer Phenotypes for gene: KMT5B were changed from Mental retardation, autosomal dominant 51 to Intellectual developmental disorder, autosomal dominant 51 MIM# 617788
Mendeliome v1.4019 TMEM251 Zornitza Stark Tag new gene name tag was added to gene: TMEM251.
Mendeliome v1.4019 TMEM251 Zornitza Stark Publications for gene: TMEM251 were set to 33252156
Mendeliome v1.4018 TMEM251 Zornitza Stark Classified gene: TMEM251 as Green List (high evidence)
Mendeliome v1.4018 TMEM251 Zornitza Stark Gene: tmem251 has been classified as Green List (High Evidence).
Mendeliome v1.4017 TMEM251 Zornitza Stark edited their review of gene: TMEM251: Added comment: PMID 40171858: reports 2 siblings from an Iranian consanguineous family and six previously reported families (8 patients, 7 unrelated families) with biallelic loss‑of‑function LYSET variants presenting with MLII‑like mucolipidosis; core features include dysostosis multiplex, coarse facial features, hepatomegaly, joint contractures, developmental delay; mouse knockout recapitulates the phenotype, supporting gene‑disease causality.

HGNC approved name is LYSET.; Changed rating: GREEN; Changed publications: 40171858
Mendeliome v1.4017 KLHL7 Lucy Spencer Mode of inheritance for gene: KLHL7 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4016 DNALI1 Zornitza Stark Marked gene: DNALI1 as ready
Mendeliome v1.4016 DNALI1 Zornitza Stark Gene: dnali1 has been classified as Green List (High Evidence).
Mendeliome v1.4016 DNALI1 Zornitza Stark Classified gene: DNALI1 as Green List (high evidence)
Mendeliome v1.4016 DNALI1 Zornitza Stark Gene: dnali1 has been classified as Green List (High Evidence).
Mendeliome v1.4015 DNALI1 Zornitza Stark gene: DNALI1 was added
gene: DNALI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNALI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNALI1 were set to 40298292; 38212584; 36792588; 36726469
Phenotypes for gene: DNALI1 were set to Spermatogenic failure, MONDO:0004983, DNALI1-related
Review for gene: DNALI1 was set to GREEN
Added comment: PMIDs 36726469, 36792588, 38212584 and 40298292 report four unrelated individuals from four families with biallelic loss‑of‑function DNALI1 variants (c.691_693del, c.663_666del, c.464‑1G>A, c.490dup) causing male infertility characterised by severe asthenozoospermia/asthénoteratozoospermia. The variants segregate as autosomal recessive and functional studies—including a mouse knockout recapitulating infertility, TEM showing loss of inner dynein arms, immunofluorescence loss of DNALI1 protein, and a minigene splicing assay demonstrating exon skipping—support loss‑of‑function as the disease mechanism.
Sources: Literature
Mendeliome v1.4014 KLHL24 Lucy Spencer Phenotypes for gene: KLHL24 were changed from Epidermolysis bullosa simplex, generalized, with scarring and hair loss OMIM#617294; dilated cardiomyopathy; Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, MIM# 620236 to Epidermolysis bullosa simplex 6, generalized intermediate, with or without cardiomyopathy MIM# 617294; Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, MIM# 620236
Mendeliome v1.4013 KLF7 Lucy Spencer Phenotypes for gene: KLF7 were changed from Intellectual disability to Neurodevelopmental disorder (MONDO:0700092), KLF7-related
Mendeliome v1.4012 KLF10 Lucy Spencer Phenotypes for gene: KLF10 were changed from HCM to Hypertrophic cardiomyopathy MONDO:0005045, KLF10-related
Mendeliome v1.4011 ATP5B Zornitza Stark Phenotypes for gene: ATP5B were changed from Inherited dystonia, MONDO:0044807, ATP5B-related to Inherited dystonia, MONDO:0044807, ATP5B-related; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Mendeliome v1.4010 KLC4 Lucy Spencer Phenotypes for gene: KLC4 were changed from Complicated hereditary spastic paraplegia to Neurodegeneration, early-childhood-onset, with retinitis pigmentosa, sensorineural hearing loss, and demyelinating peripheral neuropathy, MIM# 621129
Mendeliome v1.4009 ATP5B Zornitza Stark Publications for gene: ATP5B were set to 36860166; 36239646
Mendeliome v1.4008 ATP5B Zornitza Stark edited their review of gene: ATP5B: Added comment: PMID 40276935 reports another individual with a heterozygous splice‑donor variant c.1074+1G>T causing cerebral palsy with generalized dystonia.; Changed publications: 36860166, 36239646, 40276935; Changed phenotypes: Inherited dystonia, MONDO:0044807, ATP5B-related, Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Mendeliome v1.4008 KLB Lucy Spencer Phenotypes for gene: KLB were changed from Hypogonadotropic hypogonadism to Hypogonadotropic hypogonadism MONDO:0018555, KLB-related
Mendeliome v1.4007 KIRREL3 Lucy Spencer Phenotypes for gene: KIRREL3 were changed from Intellectual disability to Intellectual disability MONDO:0001071, KIRREL3-related
Mendeliome v1.4006 KIF5B Lucy Spencer Phenotypes for gene: KIF5B were changed from osteogenesis imperfecta, MONDO:0019019; Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia to osteogenesis imperfecta, MONDO:0019019, KIF5B-related; Skeletal dysplasia, MONDO:0018230, KIF5B-related
Mendeliome v1.4005 GCM2 Chirag Patel Phenotypes for gene: GCM2 were changed from Hyperparathyroidism 4, OMIM #617343 to Hyperparathyroidism 4, OMIM #617343; Hypoparathyroidism, familial isolated 2, OMIM #618883
Mendeliome v1.4004 GCM2 Chirag Patel Publications for gene: GCM2 were set to 27745835
Mendeliome v1.4003 GCM2 Chirag Patel Mode of inheritance for gene: GCM2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4002 CFAP43 Zornitza Stark Phenotypes for gene: CFAP43 were changed from Hydrocephalus, normal pressure, 1 236690; Spermatogenic failure 19 617592 to Spermatogenic failure 19 MONDO:0054723
Mendeliome v1.4001 CFAP43 Zornitza Stark Publications for gene: CFAP43 were set to PMID: 31884020; 28552195; 31004071; 29449551
Mendeliome v1.4000 CFAP43 Zornitza Stark Mode of inheritance for gene: CFAP43 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3999 CFAP43 Zornitza Stark Classified gene: CFAP43 as Green List (high evidence)
Mendeliome v1.3999 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Mendeliome v1.3998 CFAP43 Zornitza Stark changed review comment from: Recent publications (PMIDs 28552195, 29277146, 29449551, 34089056, 34100391, 34529793, 36960497, 38745955, 40376536, 41341611) add >25 unrelated families with biallelic CFAP43 loss‑of‑function or damaging missense variants causing multiple morphological abnormalities of the sperm flagella (MMAF) and male infertility, supported by detailed semen analyses, segregation in parents, and functional mouse knockout or patient‑cell studies.

DEFINITIVE by ClinGen for this association.

Note association with PCD is DISPUTED.

Weak evidence for association with hydrocephalus.; to: Recent publications (PMIDs 28552195, 29277146, 29449551, 34089056, 34100391, 34529793, 36960497, 38745955, 40376536, 41341611) add >25 unrelated families with biallelic CFAP43 loss‑of‑function or damaging missense variants causing multiple morphological abnormalities of the sperm flagella (MMAF) and male infertility, supported by detailed semen analyses, segregation in parents, and functional mouse knockout or patient‑cell studies.

DEFINITIVE by ClinGen for this association.

Note association with PCD is DISPUTED.

LIMITED for association with hydrocephalus.
Mendeliome v1.3998 CFAP43 Zornitza Stark edited their review of gene: CFAP43: Added comment: Recent publications (PMIDs 28552195, 29277146, 29449551, 34089056, 34100391, 34529793, 36960497, 38745955, 40376536, 41341611) add >25 unrelated families with biallelic CFAP43 loss‑of‑function or damaging missense variants causing multiple morphological abnormalities of the sperm flagella (MMAF) and male infertility, supported by detailed semen analyses, segregation in parents, and functional mouse knockout or patient‑cell studies.

DEFINITIVE by ClinGen for this association.

Note association with PCD is DISPUTED.

Weak evidence for association with hydrocephalus.; Changed rating: GREEN; Changed publications: 28552195, 29277146, 29449551, 34089056, 34100391, 34529793, 36960497, 38745955, 40376536, 41341611; Changed phenotypes: Spermatogenic failure 19 MONDO:0054723
Mendeliome v1.3998 GCM2 Chirag Patel reviewed gene: GCM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27745835, 35038313, 20190276; Phenotypes: Hyperparathyroidism 4, OMIM #617343, Hypoparathyroidism, familial isolated 2, OMIM #618883; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3998 IL18BP Zornitza Stark changed review comment from: PMID 41334112 Reports 3 individuals from 1 unrelated Egyptian family with a homozygous frameshift c.15_16del causing loss‑of‑function IL‑18BP. Two siblings (P1, P2) suffered fatal HAV‑induced fulminant viral hepatitis, while a third sibling (P3) experienced self‑healing CMV/EBV hepatitis. Autosomal recessive inheritance with complete penetrance is shown by carrier parents and heterozygous healthy siblings. In vitro assays demonstrate absence of IL‑18BP protein and loss of IL‑18 neutralisation.; to: PMID 41334112 Reports 3 individuals from 1 unrelated Egyptian family with a homozygous frameshift c.15_16del causing loss‑of‑function IL‑18BP. Two siblings (P1, P2) suffered fatal HAV‑induced fulminant viral hepatitis, while a third sibling (P3) experienced self‑healing CMV/EBV hepatitis.
Mendeliome v1.3998 IL18BP Zornitza Stark Classified gene: IL18BP as Amber List (moderate evidence)
Mendeliome v1.3998 IL18BP Zornitza Stark Gene: il18bp has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3997 IL18BP Zornitza Stark edited their review of gene: IL18BP: Added comment: PMID 41334112 Reports 3 individuals from 1 unrelated Egyptian family with a homozygous frameshift c.15_16del causing loss‑of‑function IL‑18BP. Two siblings (P1, P2) suffered fatal HAV‑induced fulminant viral hepatitis, while a third sibling (P3) experienced self‑healing CMV/EBV hepatitis. Autosomal recessive inheritance with complete penetrance is shown by carrier parents and heterozygous healthy siblings. In vitro assays demonstrate absence of IL‑18BP protein and loss of IL‑18 neutralisation.; Changed rating: AMBER; Changed publications: 41334112; Changed phenotypes: {Hepatitis, fulminant viral, susceptibility to} 618549
Mendeliome v1.3997 NOP58 Zornitza Stark Marked gene: NOP58 as ready
Mendeliome v1.3997 NOP58 Zornitza Stark Gene: nop58 has been classified as Red List (Low Evidence).
Mendeliome v1.3997 NOP58 Zornitza Stark gene: NOP58 was added
gene: NOP58 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOP58 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOP58 were set to 41383020
Phenotypes for gene: NOP58 were set to Neurodevelopmental disorder, MONDO:0700092, NOP58-related
Review for gene: NOP58 was set to RED
Added comment: PMID 41383020 reports a single individual with homozygous hypomorphic loss‑of‑function synonymous variant c.516G>A in NOP58 presenting with severe neurodevelopmental disorder characterized by global developmental delay, microcephaly, early‑onset seizures, facial dysmorphism, and brain structural anomalies. Functional studies in patient fibroblasts demonstrated exon 7 skipping, ~12 % residual NOP58 protein, reduced fibrillarin, altered nucleolar morphology, decreased box C/D snoRNAs, and impaired pre‑rRNA maturation.
Sources: Literature
Mendeliome v1.3996 PRDX3 Zornitza Stark Phenotypes for gene: PRDX3 were changed from Cerebellar ataxia MONDO:0000437, PRDX3-related to Cerebellar ataxia MONDO:0000437, PRDX3-related; Corneal dystrophy, punctiform and polychromatic pre-Descemet MIM#619871
Mendeliome v1.3995 PRDX3 Zornitza Stark Publications for gene: PRDX3 were set to PMID: 33889951
Mendeliome v1.3994 PRDX3 Zornitza Stark Mode of inheritance for gene: PRDX3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3993 PRDX3 Zornitza Stark reviewed gene: PRDX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31782998, 34369396; Phenotypes: Corneal dystrophy, punctiform and polychromatic pre-Descemet 619871; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3993 SLC25A4 Sangavi Sivagnanasundram Added comment: Comment on publications: Addition of AD publications
Mendeliome v1.3993 SLC25A4 Sangavi Sivagnanasundram Publications for gene: SLC25A4 were set to 30046662; 30013777; 29654543; 28823815
Mendeliome v1.3992 SLC25A4 Sangavi Sivagnanasundram reviewed gene: SLC25A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21519523, 27693233; Phenotypes: Leigh syndrome MONDO:0009723, autosomal dominant progressive external ophthalmoplegia MONDO:0008003; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3992 UNC45A Zornitza Stark Tag 5'UTR tag was added to gene: UNC45A.
Mendeliome v1.3992 UNC45A Zornitza Stark Publications for gene: UNC45A were set to 29429573; 35575086; 36699472; 37328071, 39887522; 40125554; 40129845; 32013205
Mendeliome v1.3991 UNC45A Zornitza Stark Publications for gene: UNC45A were set to 29429573
Mendeliome v1.3990 UNC45A Zornitza Stark edited their review of gene: UNC45A: Added comment: PMIDs 29429573, 35575086, 36699472, 37328071, 39887522, 40125554, 40129845, 32013205 add 33 unrelated families to the previously reviewed three families, bringing the total to 37 unrelated families. Eleven families present with osteo‑oto‑hepato‑enteric (O2HE) syndrome (neonatal cholestasis, intractable diarrhea, bone fragility, sensorineural hearing loss) and carry loss‑of‑function or protein‑unstable missense variants. Functional validation (Western blot, zebrafish morpholino knock‑down, rescue experiments, CRISPR‑KO in Caco‑2/U2OS cells) demonstrates pathogenicity. Twenty‑five families have Aagenaes syndrome (lymphedema‑cholestasis syndrome) caused by a recurrent 5′‑UTR regulatory variant (c.-98G>T) plus loss‑of‑function exonic alleles, with reduced UNC45A expression confirmed in patient blood and CRISPR‑edited cells.; Changed publications: 29429573, 35575086, 36699472, 37328071, 39887522, 40125554, 40129845, 32013205
Mendeliome v1.3990 Chirag Patel Copied gene KIF24 from panel Skeletal dysplasia
Mendeliome v1.3990 KIF24 Chirag Patel gene: KIF24 was added
gene: KIF24 was added to Mendeliome. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KIF24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF24 were set to 35748595
Phenotypes for gene: KIF24 were set to Skeletal dysplasia MONDO:0018230, KIF24 related
Mendeliome v1.3989 SCN1A Zornitza Stark Publications for gene: SCN1A were set to 30368457; 12754708; 25754450; 32928894; 29543227
Mendeliome v1.3988 SCN1A Zornitza Stark Mode of inheritance for gene: SCN1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3987 SCN1A Zornitza Stark edited their review of gene: SCN1A: Added comment: PMID 40120363 reviews 16 published cases with biallelic variants and reports another 2: 9/18 (50 %) were diagnosed with Dravet syndrome and 6/18 (33 %) with GEFS+. The mean age of seizure onset was 7 months (range 3-19 months). Phenotypes ranged from intact neurodevelopment with controlled epilepsy to profound developmental delay and refractory epilepsy.; Changed publications: 29543227, 40120363; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3987 MAPK8IP3 Zornitza Stark Publications for gene: MAPK8IP3 were set to 30612693
Mendeliome v1.3986 MAPK8IP3 Zornitza Stark edited their review of gene: MAPK8IP3: Added comment: PMID 37462082 reports single individual with compound het variants and a severe congenital hypotonia.; Changed publications: 30612693, 30945334, 37462082
Mendeliome v1.3986 EMC10 Zornitza Stark Publications for gene: EMC10 were set to 32869858
Mendeliome v1.3985 EMC10 Zornitza Stark edited their review of gene: EMC10: Added comment: PMIDs 35684946, 37318954, 40150819 report 10 additional unrelated families with loss‑of‑function EMC10 variants; Changed publications: 32869858, 33531666, 35684946, 37318954, 40150819
Mendeliome v1.3985 UNC13A Zornitza Stark Phenotypes for gene: UNC13A were changed from Neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, MIM# 621456; Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MIM# 621455 to Neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, MIM# 621456; Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MIM# 621455; Intellectual development disorder with seizures and dysmorphic facies, MIM# 621457
Mendeliome v1.3984 UNC13A Zornitza Stark edited their review of gene: UNC13A: Changed phenotypes: Neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, MIM# 621456, Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MIM# 621455, Intellectual development disorder with seizures and dysmorphic facies, MIM# 621457
Mendeliome v1.3984 UNC13A Zornitza Stark Phenotypes for gene: UNC13A were changed from neurodevelopmental disorder MONDO#0700092, UNC13A-related; Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MIM# 621455 to Neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, MIM# 621456; Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MIM# 621455
Mendeliome v1.3983 UNC13A Zornitza Stark edited their review of gene: UNC13A: Changed phenotypes: Neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, MIM# 621456, Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MIM# 621455
Mendeliome v1.3983 UNC13A Zornitza Stark Phenotypes for gene: UNC13A were changed from Congenital myasthenia; dyskinesia; autism; developmental delay; neurodevelopmental disorder MONDO#0700092, UNC13A-related to neurodevelopmental disorder MONDO#0700092, UNC13A-related; Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MIM# 621455
Mendeliome v1.3982 UNC13A Zornitza Stark Publications for gene: UNC13A were set to 27648472; 28192369
Mendeliome v1.3981 UNC13A Zornitza Stark edited their review of gene: UNC13A: Added comment: PMID 41125872 reports 48 individuals with neurodevelopmental disorders and UNC13A variants. Of these, 20 classified as pathogenic. Of these 6 individuals had biallelic variants and presented with severe-to-profound GDD or intellectual disability, hypotonia and seizures of different types (largely controllable with medication) or death in early childhood caused by respiratory failure after pneumonia in one case. Mechanism for this subgroup is LoF with carrier parents unaffected.

A second group of 13 patients (21 months to 32 years old) harboured pathogenic, heterozygous de novo missense variants with multiple substitutions at amino acids 808, 811 and 814 (hinge region). They presented with variable degrees of GDD, hypotonia, seizures of different types (mainly refractory to treatment) and typically exhibited ataxia, tremor or dyskinetic movements rarely observed in other patients.

Also a family identified with at least four affected members across two generations (4 years to 35 years old) harbouring a pathogenic heterozygous missense variant (C587F) that caused learning difficulties to mild–moderate intellectual disability as well as controlled seizures.

Three different types of mechanism of pathogenicity proposed.; Changed rating: GREEN; Changed publications: 27648472, 28192369, 41125872; Changed phenotypes: neurodevelopmental disorder MONDO#0700092, UNC13A-related, Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MIM# 621455
Mendeliome v1.3981 WDR83 Chirag Patel gene: WDR83 was added
gene: WDR83 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR83 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WDR83 were set to 41381792
Phenotypes for gene: WDR83 were set to Neurodevelopmental disorder, MONDO:0700092, WDR83-related
Mode of pathogenicity for gene: WDR83 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: WDR83 was set to RED
Added comment: 1 individual from 1 unrelated family with a de novo heterozygous missense variant (p.L218P) in WDR83 gene. Clinical presentation of a neurodevelopmental disorder characterised by global developmental delay, intellectual disability, growth retardation and dysmorphic facial features. WDR83 encodes a WD‑repeat scaffold protein (MORG1) that regulates MAPK/ERK signalling, HIF‑1α degradation, cell polarity and autophagy.

In vivo, acute expression via in utero electroporation promoted premature cell cycle exit of neural stem cells, impaired cortical neuron migration, and disrupted dendritic arborization, whereas axonal projections to the contralateral hemisphere remained unaffected. Cortical neurons expressing WDR83-L218P exhibited reduced spine head diameter. In vitro, WDR83-L218P expression inhibited axon elongation in primary cultured hippocampal neurons. The variant is suspected to exert a dominant-negative effect.
Sources: Literature
Mendeliome v1.3980 COL2A1 Zornitza Stark Phenotypes for gene: COL2A1 were changed from Achondrogenesis, type II or hypochondrogenesis 200610; Avascular necrosis of the femoral head 608805; Czech dysplasia 609162; Epiphyseal dysplasia, multiple, with myopia and deafness 132450; Kniest dysplasia 156550; Legg-Calve-Perthes disease 150600; Osteoarthritis with mild chondrodysplasia 604864; Platyspondylic skeletal dysplasia, Torrance type 151210; SED congenita 183900; SMED Strudwick type 184250; Spondyloepiphyseal dysplasia, Stanescu type 616583; Spondyloperipheral dysplasia 271700; Stickler sydrome, type I, nonsyndromic ocular 609508; Stickler syndrome, type I 108300; Vitreoretinopathy with phalangeal epiphyseal dysplasia to Type 2 collagenopathy MONDO:0022800
Mendeliome v1.3979 COL2A1 Zornitza Stark Publications for gene: COL2A1 were set to 15895462; 17721977; 27234559; 20179744
Mendeliome v1.3978 COL2A1 Zornitza Stark Mode of inheritance for gene: COL2A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3977 COL2A1 Zornitza Stark reviewed gene: COL2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31755234; Phenotypes: spondyloepiphyseal dysplasia congenita MONDO:0008471; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3977 NDUFB7 Zornitza Stark Publications for gene: NDUFB7 were set to 33502047; 27626371
Mendeliome v1.3976 NDUFB7 Zornitza Stark edited their review of gene: NDUFB7: Changed publications: 40025060
Mendeliome v1.3976 NDUFB7 Zornitza Stark Classified gene: NDUFB7 as Green List (high evidence)
Mendeliome v1.3976 NDUFB7 Zornitza Stark Gene: ndufb7 has been classified as Green List (High Evidence).
Mendeliome v1.3975 NDUFB7 Zornitza Stark edited their review of gene: NDUFB7: Added comment: PMID 40025060 reports second individual with compound heterozygous NM_004146.5:c.133_135del and NM_004146.5:c.311G>C variants presenting with lactic acidosis, premature birth, growth deficiency, ventral hernia, brain MRI pons abnormalities, developmental delay, and mild intellectual disability. Patient fibroblasts show Complex I assembly deficiency; zebrafish knockdown of ndufb7 reproduces brain ventricle and neuronal defects, elevated lactate.

Two families only but strong biological candidate with good functional data from different systems.; Changed rating: GREEN
Mendeliome v1.3975 FIBP Zornitza Stark Classified gene: FIBP as Green List (high evidence)
Mendeliome v1.3975 FIBP Zornitza Stark Gene: fibp has been classified as Green List (High Evidence).
Mendeliome v1.3974 FIBP Zornitza Stark edited their review of gene: FIBP: Added comment: Beyond the two families previously reviewed (PMIDs 26660953; 27183861), four additional studies (PMIDs 36919607, 37218527, 37876348, 40099975) contribute four new unrelated families (total six unrelated families, nine patients) with a consistent autosomal‑recessive overgrowth syndrome. All six families have biallelic loss‑of‑function FIBP variants (nonsense or frameshift leading to NMD). Detailed clinical descriptions include overgrowth, macrocephaly, facial dysmorphism, developmental delay/intellectual disability, renal dysplasia and, in two families, early‑onset tumor predisposition. Segregation analyses confirm recessive inheritance in every case. Functional work (RT‑qPCR, fibroblast proliferation assays, mouse embryonic expression) demonstrates reduced FIBP expression and increased cell proliferation, supporting pathogenicity.; Changed rating: GREEN; Changed publications: 40099975, 37876348, 36919607, 27183861, 26660953
Mendeliome v1.3974 DPH2 Zornitza Stark Classified gene: DPH2 as Green List (high evidence)
Mendeliome v1.3974 DPH2 Zornitza Stark Gene: dph2 has been classified as Green List (High Evidence).
Mendeliome v1.3973 DPH2 Zornitza Stark edited their review of gene: DPH2: Added comment: Third family reported with biallelic LoF variant c.1429C>T (p.Arg477*) presenting with developmental delay, proportionate short stature, sparse hair, dysmorphic facial features, hypotonia, seizures, neuroimaging abnormalities, and behavioural issues.; Changed rating: GREEN; Changed publications: 40130534
Mendeliome v1.3973 WASHC3 Zornitza Stark Publications for gene: WASHC3 were set to DOI: https://doi.org/10.1016/j.gimo.2024.101915
Mendeliome v1.3972 WASHC3 Zornitza Stark edited their review of gene: WASHC3: Changed publications: 40129681
Mendeliome v1.3972 MCM2 Zornitza Stark Publications for gene: MCM2 were set to 26196677
Mendeliome v1.3971 MCM2 Zornitza Stark edited their review of gene: MCM2: Added comment: Three additional families reported with missense variants. However, variants not segregated in two of the individuals; the variants reported in 35652205 was inherited from a mildly affected parent. The reported variants are present in gnomAD.

Given lack of additional supporting evidence and gnomAD frequencies, retain RED rating.; Changed publications: 26196677, 35652205, 40069133
Mendeliome v1.3971 SEC24C Zornitza Stark Marked gene: SEC24C as ready
Mendeliome v1.3971 SEC24C Zornitza Stark Gene: sec24c has been classified as Red List (Low Evidence).
Mendeliome v1.3971 SEC24C Zornitza Stark gene: SEC24C was added
gene: SEC24C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEC24C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC24C were set to 40131364
Phenotypes for gene: SEC24C were set to Neurodevelopmental disorder, MONDO:0700092, SEC24C-related
Review for gene: SEC24C was set to RED
Added comment: PMID 40131364 reports 4 individuals from a consanguineous Turkish family with biallelic loss-of-function frameshift c.333del (p.Ser112Profs*115) variant presenting with neonatal‑onset severe syndromic epileptic encephalopathy, congenital cataracts, primary microcephaly, macrocytic anaemia, sensorineural hearing loss, liver dysfunction and dysmorphic facial features. The variant segregates with autosomal recessive inheritance and functional studies in patient fibroblasts and zebrafish knockouts demonstrate >90% loss of SEC24C expression, impaired ER‑Golgi trafficking and recapitulation of cataract and neurodevelopmental phenotypes.
Sources: Literature
Mendeliome v1.3970 ARAF Zornitza Stark Marked gene: ARAF as ready
Mendeliome v1.3970 ARAF Zornitza Stark Gene: araf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3970 Zornitza Stark Copied gene ARAF from panel Lymphoedema_nonsyndromic
Mendeliome v1.3970 ARAF Zornitza Stark gene: ARAF was added
gene: ARAF was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ARAF was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ARAF were set to 31263281
Phenotypes for gene: ARAF were set to Lymphatic malformation, MONDO:0019313, ARAF-related
Mode of pathogenicity for gene: ARAF was set to Other
Mendeliome v1.3969 CAMK2G Elena Savva Phenotypes for gene: CAMK2G were changed from Mental retardation, autosomal dominant 59, MIM# 618522 to Intellectual developmental disorder, autosomal dominant 59 MIM# 618522
Mendeliome v1.3968 CEL Seb Lunke Mode of pathogenicity for gene: CEL was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v1.3967 CEL Seb Lunke Tag technically challenging tag was added to gene: CEL.
Mendeliome v1.3967 CEL Seb Lunke Added comment: Comment on mode of pathogenicity: Dominant Negative Gain-of-Function experimentally established
Mendeliome v1.3967 CEL Seb Lunke Mode of pathogenicity for gene: CEL was changed from to Other
Mendeliome v1.3966 CEL Seb Lunke Publications for gene: CEL were set to 24062244; 21784842; 19760265; 18544793; 17989309; 16369531; 29233499; 27650499
Mendeliome v1.3965 CEL Seb Lunke Classified gene: CEL as Green List (high evidence)
Mendeliome v1.3965 CEL Seb Lunke Added comment: Comment on list classification: Remains technically challenging but most of critical region (First 5 repeats of exon 11 VNTR) are callable on short read data.
Mendeliome v1.3965 CEL Seb Lunke Gene: cel has been classified as Green List (High Evidence).
Mendeliome v1.3964 Seb Lunke Added reviews for gene CEL from panel Genomic screening in children: BabyScreen+
Mendeliome v1.3963 APBB1 Zornitza Stark Marked gene: APBB1 as ready
Mendeliome v1.3963 APBB1 Zornitza Stark Gene: apbb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3963 APBB1 Zornitza Stark Classified gene: APBB1 as Amber List (moderate evidence)
Mendeliome v1.3963 APBB1 Zornitza Stark Gene: apbb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3962 APBB1 Zornitza Stark gene: APBB1 was added
gene: APBB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: APBB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: APBB1 were set to 40151319
Phenotypes for gene: APBB1 were set to Infertility disorder, MONDO:0005047, APBB1-related
Review for gene: APBB1 was set to AMBER
Added comment: PMID 40151319 reports 9 individuals from 9 unrelated families with heterozygous variants (missense, nonsense, frameshift) in APBB1 presenting with non‑obstructive azoospermia (NOA). The study provides mouse conditional knockout and human spermatogonial stem cell knock‑down functional data supporting a role for APBB1 loss of function in spermatogenic failure. Missing segregation data and at least 2 of the reported variants are present at high frequencies in gnomAD.
Sources: Literature
Mendeliome v1.3961 Bryony Thompson Copied STR ZIC2_HPE5_GCN from panel Repeat Disorders
Mendeliome v1.3961 ZIC2_HPE5_GCN Bryony Thompson STR: ZIC2_HPE5_GCN was added
STR: ZIC2_HPE5_GCN was added to Mendeliome. Sources: Expert Review Green,Expert list
paediatric-onset tags were added to STR: ZIC2_HPE5_GCN.
Mode of inheritance for STR: ZIC2_HPE5_GCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: ZIC2_HPE5_GCN were set to 11285244; 33811808
Phenotypes for STR: ZIC2_HPE5_GCN were set to Holoprosencephaly 5 MIM#609637
Mendeliome v1.3960 Bryony Thompson Copied STR XYLT1_DBQD2_GGC from panel Repeat Disorders
Mendeliome v1.3960 XYLT1_DBQD2_GGC Bryony Thompson STR: XYLT1_DBQD2_GGC was added
STR: XYLT1_DBQD2_GGC was added to Mendeliome. Sources: Expert Review Green,Expert list
paediatric-onset tags were added to STR: XYLT1_DBQD2_GGC.
Mode of inheritance for STR: XYLT1_DBQD2_GGC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: XYLT1_DBQD2_GGC were set to 30554721
Phenotypes for STR: XYLT1_DBQD2_GGC were set to Desbuquois dysplasia 2 MIM#615777
Mendeliome v1.3959 Bryony Thompson Copied STR VWA1_HMNMYO_GCGCGGAGCG from panel Repeat Disorders
Mendeliome v1.3959 VWA1_HMNMYO_GCGCGGAGCG Bryony Thompson STR: VWA1_HMNMYO_GCGCGGAGCG was added
STR: VWA1_HMNMYO_GCGCGGAGCG was added to Mendeliome. Sources: Expert Review Green,Literature
paediatric-onset tags were added to STR: VWA1_HMNMYO_GCGCGGAGCG.
Mode of inheritance for STR: VWA1_HMNMYO_GCGCGGAGCG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: VWA1_HMNMYO_GCGCGGAGCG were set to 33559681; 33459760
Phenotypes for STR: VWA1_HMNMYO_GCGCGGAGCG were set to Neuropathy, hereditary motor, with myopathic features MIM#619216
Mendeliome v1.3958 Bryony Thompson Copied STR TCF4_FECD3_CTG from panel Repeat Disorders
Mendeliome v1.3958 TCF4_FECD3_CTG Bryony Thompson STR: TCF4_FECD3_CTG was added
STR: TCF4_FECD3_CTG was added to Mendeliome. Sources: Expert Review Green,Expert list
adult-onset tags were added to STR: TCF4_FECD3_CTG.
Mode of inheritance for STR: TCF4_FECD3_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: TCF4_FECD3_CTG were set to 25722209; 24255041
Phenotypes for STR: TCF4_FECD3_CTG were set to Corneal dystrophy, Fuchs endothelial, 3 MIM#613267
Mendeliome v1.3957 Bryony Thompson Copied STR TBX1_TOF_GCN from panel Repeat Disorders
Mendeliome v1.3957 TBX1_TOF_GCN Bryony Thompson STR: TBX1_TOF_GCN was added
STR: TBX1_TOF_GCN was added to Mendeliome. Sources: Expert Review Green,Literature
paediatric-onset tags were added to STR: TBX1_TOF_GCN.
Mode of inheritance for STR: TBX1_TOF_GCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: TBX1_TOF_GCN were set to 19948535; 11748311
Phenotypes for STR: TBX1_TOF_GCN were set to Tetralogy of Fallot MIM#187500
Mendeliome v1.3956 Bryony Thompson Copied STR TAF1_XDP_CCCTCT from panel Repeat Disorders
Mendeliome v1.3956 TAF1_XDP_CCCTCT Bryony Thompson STR: TAF1_XDP_CCCTCT was added
STR: TAF1_XDP_CCCTCT was added to Mendeliome. Sources: Expert Review Green,Expert list
founder, adult-onset tags were added to STR: TAF1_XDP_CCCTCT.
Mode of inheritance for STR: TAF1_XDP_CCCTCT was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: TAF1_XDP_CCCTCT were set to 17273961; 29229810
Phenotypes for STR: TAF1_XDP_CCCTCT were set to Dystonia-Parkinsonism, X-linked MIM#314250
Mendeliome v1.3955 Bryony Thompson Copied STR SOX3_PHPX_GCN from panel Repeat Disorders
Mendeliome v1.3955 SOX3_PHPX_GCN Bryony Thompson STR: SOX3_PHPX_GCN was added
STR: SOX3_PHPX_GCN was added to Mendeliome. Sources: Expert Review Green,Expert list
paediatric-onset tags were added to STR: SOX3_PHPX_GCN.
Mode of inheritance for STR: SOX3_PHPX_GCN was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: SOX3_PHPX_GCN were set to 12428212; 15800844; 33811808; 23505376; 19654509
Phenotypes for STR: SOX3_PHPX_GCN were set to Intellectual disability, X-linked, with isolated growth hormone deficiency MIM#300123; Panhypopituitarism, X-linked MIM#312000
Mendeliome v1.3954 Bryony Thompson Copied STR PRDM12_HSAN8_GCC from panel Repeat Disorders
Mendeliome v1.3954 PRDM12_HSAN8_GCC Bryony Thompson STR: PRDM12_HSAN8_GCC was added
STR: PRDM12_HSAN8_GCC was added to Mendeliome. Sources: Expert Review Green,Literature
paediatric-onset tags were added to STR: PRDM12_HSAN8_GCC.
Mode of inheritance for STR: PRDM12_HSAN8_GCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: PRDM12_HSAN8_GCC were set to 26005867
Phenotypes for STR: PRDM12_HSAN8_GCC were set to Neuropathy, hereditary sensory and autonomic, type VIII MIM#616488
Mendeliome v1.3953 Bryony Thompson Copied STR PHOX2B_CCHS_GCN from panel Repeat Disorders
Mendeliome v1.3953 PHOX2B_CCHS_GCN Bryony Thompson STR: PHOX2B_CCHS_GCN was added
STR: PHOX2B_CCHS_GCN was added to Mendeliome. Sources: Expert Review Green,Expert list
paediatric-onset tags were added to STR: PHOX2B_CCHS_GCN.
Mode of inheritance for STR: PHOX2B_CCHS_GCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: PHOX2B_CCHS_GCN were set to 12640453; 34012823; 20301600; 18798833
Phenotypes for STR: PHOX2B_CCHS_GCN were set to Central hypoventilation syndrome, congenital, with or without Hirschsprung disease MIM#209880
Mendeliome v1.3952 Bryony Thompson Copied STR PABPN1_OPMD_GCN from panel Repeat Disorders
Mendeliome v1.3952 PABPN1_OPMD_GCN Bryony Thompson STR: PABPN1_OPMD_GCN was added
STR: PABPN1_OPMD_GCN was added to Mendeliome. Sources: Expert Review Green,Expert list
adult-onset tags were added to STR: PABPN1_OPMD_GCN.
Mode of inheritance for STR: PABPN1_OPMD_GCN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for STR: PABPN1_OPMD_GCN were set to 9462747; 20301305
Phenotypes for STR: PABPN1_OPMD_GCN were set to Oculopharyngeal muscular dystrophy MIM#164300
Mendeliome v1.3951 Bryony Thompson Copied STR NUTM2B-AS1_OPDM_CCG from panel Repeat Disorders
Mendeliome v1.3951 NUTM2B-AS1_OPDM_CCG Bryony Thompson STR: NUTM2B-AS1_OPDM_CCG was added
STR: NUTM2B-AS1_OPDM_CCG was added to Mendeliome. Sources: Expert Review Green,Literature
adult-onset tags were added to STR: NUTM2B-AS1_OPDM_CCG.
Mode of inheritance for STR: NUTM2B-AS1_OPDM_CCG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NUTM2B-AS1_OPDM_CCG were set to 31332380
Phenotypes for STR: NUTM2B-AS1_OPDM_CCG were set to Oculopharyngeal myopathy with leukoencephalopathy 1 MIM#618637
Mendeliome v1.3950 Bryony Thompson Copied STR LRP12_OPDM1_CGG from panel Repeat Disorders
Mendeliome v1.3950 LRP12_OPDM1_CGG Bryony Thompson STR: LRP12_OPDM1_CGG was added
STR: LRP12_OPDM1_CGG was added to Mendeliome. Sources: Expert Review Green,Expert list
adult-onset tags were added to STR: LRP12_OPDM1_CGG.
Mode of inheritance for STR: LRP12_OPDM1_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: LRP12_OPDM1_CGG were set to 31332380; 34047774; 37339631
Phenotypes for STR: LRP12_OPDM1_CGG were set to Oculopharyngodistal myopathy 1 MIM#164310; Amyotrophic lateral sclerosis MONDO:0004976
Mendeliome v1.3949 Bryony Thompson Copied STR HOXD13_SPD1_GCG from panel Repeat Disorders
Mendeliome v1.3949 HOXD13_SPD1_GCG Bryony Thompson STR: HOXD13_SPD1_GCG was added
STR: HOXD13_SPD1_GCG was added to Mendeliome. Sources: Expert Review Green,Expert list
paediatric-onset tags were added to STR: HOXD13_SPD1_GCG.
Mode of inheritance for STR: HOXD13_SPD1_GCG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HOXD13_SPD1_GCG were set to 8817328; 33811808; 33533119
Phenotypes for STR: HOXD13_SPD1_GCG were set to Synpolydactyly 1 MIM#186000
Mendeliome v1.3948 Bryony Thompson Copied STR HOXA13_HFGS_GCN3 from panel Repeat Disorders
Mendeliome v1.3948 HOXA13_HFGS_GCN3 Bryony Thompson STR: HOXA13_HFGS_GCN3 was added
STR: HOXA13_HFGS_GCN3 was added to Mendeliome. Sources: Expert Review Green,Expert list
paediatric-onset tags were added to STR: HOXA13_HFGS_GCN3.
Mode of inheritance for STR: HOXA13_HFGS_GCN3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HOXA13_HFGS_GCN3 were set to 10839976; 12073020; 33811808
Phenotypes for STR: HOXA13_HFGS_GCN3 were set to Hand-foot-uterus syndrome MIM#140000
Mendeliome v1.3947 Bryony Thompson Copied STR GLS_GDPAG_GCA from panel Repeat Disorders
Mendeliome v1.3947 GLS_GDPAG_GCA Bryony Thompson STR: GLS_GDPAG_GCA was added
STR: GLS_GDPAG_GCA was added to Mendeliome. Sources: Expert Review Green,Literature
paediatric-onset tags were added to STR: GLS_GDPAG_GCA.
Mode of inheritance for STR: GLS_GDPAG_GCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: GLS_GDPAG_GCA were set to 30970188
Phenotypes for STR: GLS_GDPAG_GCA were set to Global developmental delay, progressive ataxia, and elevated glutamine MIM#618412
Mendeliome v1.3946 Bryony Thompson Copied STR FXN_FRDA_GAA from panel Repeat Disorders
Mendeliome v1.3946 FXN_FRDA_GAA Bryony Thompson STR: FXN_FRDA_GAA was added
STR: FXN_FRDA_GAA was added to Mendeliome. Sources: Expert Review Green,Expert list
paediatric-onset tags were added to STR: FXN_FRDA_GAA.
Mode of inheritance for STR: FXN_FRDA_GAA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: FXN_FRDA_GAA were set to 20301458; 8596916
Phenotypes for STR: FXN_FRDA_GAA were set to Friedreich ataxia MIM#229300
Mendeliome v1.3945 Bryony Thompson Copied STR FOXL2_BPES_GCN from panel Repeat Disorders
Mendeliome v1.3945 FOXL2_BPES_GCN Bryony Thompson STR: FOXL2_BPES_GCN was added
STR: FOXL2_BPES_GCN was added to Mendeliome. Sources: Expert Review Green,Expert list
paediatric-onset tags were added to STR: FOXL2_BPES_GCN.
Mode of inheritance for STR: FOXL2_BPES_GCN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for STR: FOXL2_BPES_GCN were set to 11468277; 33811808
Phenotypes for STR: FOXL2_BPES_GCN were set to Blepharophimosis, epicanthus inversus, and ptosis type 1 and 2 MIM#110100; Premature ovarian failure 3 MIM#608996
Mendeliome v1.3944 SUPT5H Zornitza Stark Mode of inheritance for gene: SUPT5H was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3943 SUPT5H Zornitza Stark edited their review of gene: SUPT5H: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3943 SUPT5H Zornitza Stark Marked gene: SUPT5H as ready
Mendeliome v1.3943 SUPT5H Zornitza Stark Gene: supt5h has been classified as Green List (High Evidence).
Mendeliome v1.3943 SUPT5H Zornitza Stark Classified gene: SUPT5H as Green List (high evidence)
Mendeliome v1.3943 SUPT5H Zornitza Stark Gene: supt5h has been classified as Green List (High Evidence).
Mendeliome v1.3942 SUPT5H Zornitza Stark gene: SUPT5H was added
gene: SUPT5H was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUPT5H was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SUPT5H were set to 40159794; 36945604; 36054783; 32589702
Phenotypes for gene: SUPT5H were set to Erythrocyte disorder, MONDO:0044347, SUPT5H-related
Review for gene: SUPT5H was set to GREEN
Added comment: PMID 32589702, 36054783, 36945604, 37586368, 39902717 and 40159794 collectively report >40 unrelated families with heterozygous loss‑of‑function SUPT5H variants causing a β‑thalassemia‑trait‑like phenotype (elevated HbA2, mild microcytic anemia). Variants segregate in an autosomal‑dominant pattern, LOD > 3.5 in large pedigrees, and functional assays (RNA‑splicing defects, CRISPR‑edited HSPC models) demonstrate haploinsufficiency.
Sources: Literature
Mendeliome v1.3941 FRMD4B Zornitza Stark Marked gene: FRMD4B as ready
Mendeliome v1.3941 FRMD4B Zornitza Stark Gene: frmd4b has been classified as Red List (Low Evidence).
Mendeliome v1.3941 FRMD4B Zornitza Stark gene: FRMD4B was added
gene: FRMD4B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FRMD4B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRMD4B were set to 40162949
Phenotypes for gene: FRMD4B were set to Duane retraction syndrome, MONDO:0007473, FRMD4B-related
Review for gene: FRMD4B was set to RED
Added comment: PMID 40162949 reports an individual with homozygous FRMD4B missense (c.380A>G, p.Lys127Arg) variant presenting with Duane retraction syndrome type III and syndromic features (hearing loss, developmental delay, atrial septal defect, gastrointestinal abnormalities). Zebrafish loss‑of‑function model recapitulates the cranial nerve phenotype, supporting a loss‑of‑function disease mechanism.
Sources: Literature
Mendeliome v1.3940 CRIM1 Zornitza Stark Marked gene: CRIM1 as ready
Mendeliome v1.3940 CRIM1 Zornitza Stark Gene: crim1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3940 CRIM1 Zornitza Stark Classified gene: CRIM1 as Amber List (moderate evidence)
Mendeliome v1.3940 CRIM1 Zornitza Stark Gene: crim1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3939 CRIM1 Zornitza Stark gene: CRIM1 was added
gene: CRIM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRIM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CRIM1 were set to 40114969; 33418956
Phenotypes for gene: CRIM1 were set to Microphthalmia, MONDO:0021129, CRIM1-related
Review for gene: CRIM1 was set to AMBER
Added comment: PMID 33418956 reports 1 individual, and PMID 40114969 reports 3 individuals from 3 families, all with heterozygous loss‑of‑function CRIM1 variants causing colobomatous macropthalmia with microcornea (MACOM) in an autosomal dominant pattern. Segregation is demonstrated across multiple affected relatives, and mouse and zebrafish loss‑of‑function models recapitulate the ocular phenotype, supporting haploinsufficiency as the disease mechanism. However, three of the variants are deletions of various sizes and one of the variants is present in gnomAD.
Sources: Literature
Mendeliome v1.3938 ARMC2 Zornitza Stark Marked gene: ARMC2 as ready
Mendeliome v1.3938 ARMC2 Zornitza Stark Gene: armc2 has been classified as Green List (High Evidence).
Mendeliome v1.3938 ARMC2 Zornitza Stark Classified gene: ARMC2 as Green List (high evidence)
Mendeliome v1.3938 ARMC2 Zornitza Stark Gene: armc2 has been classified as Green List (High Evidence).
Mendeliome v1.3937 ARMC2 Zornitza Stark gene: ARMC2 was added
gene: ARMC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARMC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC2 were set to 40158138; 38492154; 35543806; 30686508
Phenotypes for gene: ARMC2 were set to Spermatogenic failure 38, MIM# 618433
Review for gene: ARMC2 was set to GREEN
Added comment: ARMC2 encodes an 867‑amino‑acid armadillo‑repeat protein highly expressed in testis and implicated in assembly and stability of the central pair complex of motile cilia and sperm flagella. Ten unrelated families (ten patients) with biallelic loss‑of‑function or predicted loss‑of‑function ARMC2 variants have been reported with multiple morphological abnormalities of the sperm flagella (MMAF) causing severe asthenoteratozoospermia and male infertility; one of these families also presented with primary ciliary dyskinesia pulmonary manifestations. Supportive mouse model.
Sources: Literature
Mendeliome v1.3936 RHEB Zornitza Stark Publications for gene: RHEB were set to 31337748; 29051493
Mendeliome v1.3935 RHEB Zornitza Stark edited their review of gene: RHEB: Added comment: PMID 39993836 reports fourth individual with de novo variant c.71 T>C; p.Ile24Thr, ID and epilepsy.; Changed publications: 31337748, 29051493, 39993836
Mendeliome v1.3935 MACF1 Zornitza Stark Phenotypes for gene: MACF1 were changed from Lissencephaly 9 with complex brainstem malformation, MIM# 618325 to Lissencephaly 9 with complex brainstem malformation, MIM# 618325; Congenital myasthenic syndrome, MONDO:0018940, MACF1-related
Mendeliome v1.3934 MACF1 Zornitza Stark Publications for gene: MACF1 were set to 30471716
Mendeliome v1.3933 MACF1 Zornitza Stark Mode of pathogenicity for gene: MACF1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Mendeliome v1.3932 MACF1 Zornitza Stark Mode of inheritance for gene: MACF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3931 MACF1 Zornitza Stark edited their review of gene: MACF1: Added comment: PMIDs 37721175 and 30842214: 3 individuals reported with bi-allelic variants in this gene and a myasthenic phenotype, two congenital, one adult. Some functional data supports association.; Changed publications: 30471716, 37721175, 30842214; Changed phenotypes: Lissencephaly 9 with complex brainstem malformation, MIM# 618325, Congenital myasthenic syndrome, MONDO:0018940, MACF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3931 LIG4 Zornitza Stark Publications for gene: LIG4 were set to 11779494; 16088910; 15333585; 20133615
Mendeliome v1.3930 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3929 LIG4 Zornitza Stark edited their review of gene: LIG4: Added comment: PMID 37004747: 2 variants (p.R580Q, p.A842D) in unrelated patients associated with a dominantly inherited
familial immune-dysregulation consisting of autoimmune cytopenias, lymphoproliferation, agammaglobulinemia and adaptive immune cell infiltration into nonlymphoid organ. Reconstitution experiments and molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient.; Changed publications: 11779494, 16088910, 15333585, 20133615, 37004747; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3929 KITLG Zornitza Stark Mode of inheritance for gene: KITLG was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3928 ABCD3_OPDM_GCC Zornitza Stark Phenotypes for STR: ABCD3_OPDM_GCC were changed from Oculopharyngodistal myopathy MONDO:0025193; Oculopharyngodistal myopathy 5, MIM# 621446 to Oculopharyngodistal myopathy 5, MIM# 621446
Mendeliome v1.3927 ABCD3_OPDM_GCC Zornitza Stark Phenotypes for STR: ABCD3_OPDM_GCC were changed from Oculopharyngodistal myopathy MONDO:0025193 to Oculopharyngodistal myopathy MONDO:0025193; Oculopharyngodistal myopathy 5, MIM# 621446
Mendeliome v1.3926 ABCD3_OPDM_GCC Zornitza Stark reviewed STR: ABCD3_OPDM_GCC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Oculopharyngodistal myopathy 5, MIM# 621446; Mode of inheritance: None
Mendeliome v1.3926 RSPRY1 Zornitza Stark Publications for gene: RSPRY1 were set to 26365341
Mendeliome v1.3925 RSPRY1 Zornitza Stark Classified gene: RSPRY1 as Green List (high evidence)
Mendeliome v1.3925 RSPRY1 Zornitza Stark Gene: rspry1 has been classified as Green List (High Evidence).
Mendeliome v1.3924 RSPRY1 Zornitza Stark edited their review of gene: RSPRY1: Added comment: PMIDs 30063090, 38562122 and 39940902 add three additional unrelated families (total 5 families, 12 patients) with autosomal recessive loss‑of‑function RSPRY1 variants causing spondyloepimetaphyseal dysplasia, Faden‑Alkuraya type.; Changed rating: GREEN; Changed publications: 26365341, 30063090, 38562122, 39940902
Mendeliome v1.3924 TAX1BP3 Zornitza Stark Publications for gene: TAX1BP3 were set to 39963794
Mendeliome v1.3923 TAX1BP3 Zornitza Stark edited their review of gene: TAX1BP3: Added comment: PMID 25645515 reports 2 individuals from a consanguineous family with autosomal recessive dilated cardiomyopathy and septo‑optic dysplasia and a homozygous missense variant in TAX1BP3.; Changed publications: 39963794, 25645515
Mendeliome v1.3923 USMG5 Zornitza Stark Publications for gene: USMG5 were set to 29917077; 30240627
Mendeliome v1.3922 USMG5 Zornitza Stark edited their review of gene: USMG5: Changed rating: AMBER
Mendeliome v1.3922 USMG5 Zornitza Stark reviewed gene: USMG5: Rating: ; Mode of pathogenicity: None; Publications: 40014158; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 6 MIM#618683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3922 TERB1 Zornitza Stark Marked gene: TERB1 as ready
Mendeliome v1.3922 TERB1 Zornitza Stark Gene: terb1 has been classified as Green List (High Evidence).
Mendeliome v1.3922 TERB1 Zornitza Stark Classified gene: TERB1 as Green List (high evidence)
Mendeliome v1.3922 TERB1 Zornitza Stark Gene: terb1 has been classified as Green List (High Evidence).
Mendeliome v1.3921 TERB1 Zornitza Stark gene: TERB1 was added
gene: TERB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TERB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TERB1 were set to 38277113; 35172124; 33211200; 32741963
Phenotypes for gene: TERB1 were set to Infertility disorder, MONDO:0005047, TERB1-related
Review for gene: TERB1 was set to GREEN
Added comment: PMIDs 32741963, 33211200, 35172124 and 38277113 report a total of 5 unrelated families with biallelic loss‑of‑function or missense TERB1 variants causing male infertility (non‑obstructive azoospermia with spermatogenic arrest) and  2 unrelated families with primary female infertility (diminished ovarian reserve). The variants include frameshift, stop‑gain and missense changes; mouse Terb1 knockout recapitulates the meiotic‑arrest phenotype.
Sources: Literature
Mendeliome v1.3920 C14orf80 Zornitza Stark Publications for gene: C14orf80 were set to 39979680; 38252227
Mendeliome v1.3919 C14orf80 Zornitza Stark Classified gene: C14orf80 as Green List (high evidence)
Mendeliome v1.3919 C14orf80 Zornitza Stark Gene: c14orf80 has been classified as Green List (High Evidence).
Mendeliome v1.3918 C14orf80 Zornitza Stark reviewed gene: C14orf80: Rating: GREEN; Mode of pathogenicity: None; Publications: 30842647; Phenotypes: Primary microcephaly, MONDO:0016660; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3918 RBBP7 Zornitza Stark Marked gene: RBBP7 as ready
Mendeliome v1.3918 RBBP7 Zornitza Stark Gene: rbbp7 has been classified as Green List (High Evidence).
Mendeliome v1.3918 RBBP7 Zornitza Stark edited their review of gene: RBBP7: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.3918 RBBP7 Zornitza Stark Mode of inheritance for gene: RBBP7 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.3917 RBBP7 Zornitza Stark Classified gene: RBBP7 as Green List (high evidence)
Mendeliome v1.3917 RBBP7 Zornitza Stark Gene: rbbp7 has been classified as Green List (High Evidence).
Mendeliome v1.3916 RBBP7 Zornitza Stark gene: RBBP7 was added
gene: RBBP7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBBP7 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: RBBP7 were set to 39932629; 37843278; 35809576
Phenotypes for gene: RBBP7 were set to Infertility disorder, MONDO:0005047, RBBP7-related
Review for gene: RBBP7 was set to GREEN
Added comment: PMID 35809576, 37843278, 39932629 report 12 individuals from 11 families with X-linked loss-of-function variants presenting with non‑obstructive azoospermia (severe spermatogenic failure), including maturation arrest and, in one family, Leydig cell tumor. Clinical features include small testes, elevated FSH, absence of spermatocytes and infertility. Functional evidence from Drosophila knock‑down and rescue experiments and mouse germ‑cell line knock‑down supports a loss‑of‑function (haploinsufficiency) mechanism. No contradictory evidence has been reported.
Sources: Literature
Mendeliome v1.3915 PRMT1 Zornitza Stark Marked gene: PRMT1 as ready
Mendeliome v1.3915 PRMT1 Zornitza Stark Gene: prmt1 has been classified as Green List (High Evidence).
Mendeliome v1.3915 PRMT1 Zornitza Stark Phenotypes for gene: PRMT1 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder, MONDO:0700092, PRMT1-related
Mendeliome v1.3914 PRMT1 Zornitza Stark Classified gene: PRMT1 as Green List (high evidence)
Mendeliome v1.3914 PRMT1 Zornitza Stark Gene: prmt1 has been classified as Green List (High Evidence).
Mendeliome v1.3913 PRMT1 Zornitza Stark changed review comment from: PMID 39937650 reports four individuals from four unrelated families with heterozygous de novo missense PRMT1 variants presenting with neurodevelopmental disorder and dystonia. Functional studies demonstrated reduced protein stability and enzymatic activity, supporting a loss‑of‑function mechanism.
Sources: Literature; to: PMID 39937650 reports four individuals from four unrelated families with heterozygous de novo missense PRMT1 variants presenting with neurodevelopmental disorder and dystonia (in two). Functional studies demonstrated reduced protein stability and enzymatic activity, supporting a loss‑of‑function mechanism.

Two of the individuals had the same variant, p.Glu291Lys.

Sources: Literature
Mendeliome v1.3913 PRMT1 Zornitza Stark gene: PRMT1 was added
gene: PRMT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRMT1 were set to 39937650
Phenotypes for gene: PRMT1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: PRMT1 was set to GREEN
Added comment: PMID 39937650 reports four individuals from four unrelated families with heterozygous de novo missense PRMT1 variants presenting with neurodevelopmental disorder and dystonia. Functional studies demonstrated reduced protein stability and enzymatic activity, supporting a loss‑of‑function mechanism.
Sources: Literature
Mendeliome v1.3912 EXOSC4 Zornitza Stark Marked gene: EXOSC4 as ready
Mendeliome v1.3912 EXOSC4 Zornitza Stark Gene: exosc4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3912 EXOSC4 Zornitza Stark Classified gene: EXOSC4 as Amber List (moderate evidence)
Mendeliome v1.3912 EXOSC4 Zornitza Stark Gene: exosc4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3911 EXOSC4 Zornitza Stark gene: EXOSC4 was added
gene: EXOSC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOSC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC4 were set to 39009343; 37961665; 36344539
Phenotypes for gene: EXOSC4 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: EXOSC4 was set to AMBER
Added comment: PMID 37961665, 39009343 and 39982806 all report the same family with two affected siblings and a homozygous missense p.Leu187Pro variant. Reported clinical features include severe neurodevelopmental disorder with prenatal growth restriction, failure to thrive, global developmental delay, intracerebral/basal‑ganglia calcifications, renal failure and brain atrophy. Functional data in yeast and mammalian cells support pathogenicity. One additional family (PMID 36344539) reported with brain atrophy but limited other detail.
Sources: Literature
Mendeliome v1.3910 KDM2A Zornitza Stark Publications for gene: KDM2A were set to
Mendeliome v1.3909 KDM2A Zornitza Stark reviewed gene: KDM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 41468891; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KDM2A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3909 THBD Zornitza Stark Phenotypes for gene: THBD were changed from {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926; Bleeding disorder to Thrombophilia 12 due to thrombomodulin defect, MIM# 614486
Mendeliome v1.3908 THBD Zornitza Stark Publications for gene: THBD were set to 29500241; 19625716; 25564403; 32634856
Mendeliome v1.3907 THBD Zornitza Stark edited their review of gene: THBD: Changed publications: 29500241, 19625716, 25564403, 32634856, 39841007, 34474479; Changed phenotypes: Thrombophilia 12 due to thrombomodulin defect, MIM# 614486
Mendeliome v1.3907 THBD Zornitza Stark edited their review of gene: THBD: Added comment: Association with bleeding disorders:

PMID 39841007: identified 8 THBD variants for 6 patients with a thrombotic (C175S, A282P, L433P, P501L, G502R, and P508L) and 2 patients with a bleeding (P260A and T478I) phenotypes from a large cohort. Functional evidence supporting pathogenicity only generated for two of the variants, functional effects of L433P and potentially C175S.

PMID 34474479: single individual with homozygous missense variant, c.793T>A (p.Cys265Ser) and potentially life-threatening bleeding events.; Changed rating: GREEN; Changed phenotypes: {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926, Thrombophilia 12 due to thrombomodulin defect, MIM# 614486
Mendeliome v1.3907 TGFBI Zornitza Stark Publications for gene: TGFBI were set to 9054935
Mendeliome v1.3906 TGFBI Zornitza Stark Mode of inheritance for gene: TGFBI was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3905 TGFBI Zornitza Stark edited their review of gene: TGFBI: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3905 TGFBI Zornitza Stark edited their review of gene: TGFBI: Added comment: Multiple individuals with biallelic variants and a more severe phenotype.; Changed publications: 9054935, 33772078
Mendeliome v1.3905 PGM3 Zornitza Stark Publications for gene: PGM3 were set to 30578875; 31231132; 33098103; 30157810; 28704707; 33193641
Mendeliome v1.3905 PGM3 Zornitza Stark Publications for gene: PGM3 were set to 30578875; 31231132; 33098103; 30157810; 28704707
Mendeliome v1.3904 PGM3 Zornitza Stark edited their review of gene: PGM3: Changed publications: 30578875, 31231132, 33098103, 30157810, 28704707, 33193641
Mendeliome v1.3904 PGM3 Zornitza Stark commented on gene: PGM3: Note also PMID 33193641 proposes association between heterozygous missense variants and idiopathic focal epilepsy. However, two of the four variants are inherited from asymptomatic parents and reduced penetrance invoked. Borderline RED/AMBER for this association.
Mendeliome v1.3904 PEX19 Zornitza Stark Publications for gene: PEX19 were set to
Mendeliome v1.3903 PEX19 Zornitza Stark Mode of inheritance for gene: PEX19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3902 PEX19 Zornitza Stark reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: None; Publications: 39757991, 36931687, 29282281; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger) - MIM#614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3902 MET Zornitza Stark Phenotypes for gene: MET were changed from Arthrogryposis, distal, type 11 (MIM#620019), AD; Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884 to Arthrogryposis, distal, type 11 (MIM#620019), AD; Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884; Osteofibrous dysplasia, susceptibility to} 607278
Mendeliome v1.3901 MET Zornitza Stark Publications for gene: MET were set to 30777867
Mendeliome v1.3900 MET Zornitza Stark edited their review of gene: MET: Added comment: OSFD is characterized by radiolucent lesions located at the periosteal surface of the diaphyseal cortex, almost exclusively of the tibia and fibula. These lesions are congenital and spontaneously resolve during skeletal maturation. Three germline variants and one ?somatic variant identified in PMID 26637977, all abolished the splice inclusion of exon 14 in MET transcripts, which resulted in a MET receptor (MET(Δ14)) lacking a cytoplasmic juxtamembrane domain. Incomplete penetrance.

AMBER for this association.; Changed publications: 30777867, 26637977; Changed phenotypes: Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074, Papillary renal cell carcinoma MONDO:0017884, {Osteofibrous dysplasia, susceptibility to} 607278
Mendeliome v1.3900 ACTN2 Zornitza Stark edited their review of gene: ACTN2: Added comment: Multiple cardiac and skeletal phenotypes associated with variants in this gene.

Association with cardiomyopathy is established as is the adult-onset dominant skeletal myopathy.

There are only 2 unrelated individuals reported with congenital multiple‑structured‑core disease (MsCD), with de novo heterozygous variants.

The recessive adult‑onset ACTN2‑related myopathy has been reported in 5 families (7 patients) but all with homozygous p.Arg506Gly.

These two associations are AMBER.; Changed phenotypes: Myopathy, distal, 6, adult onset MIM#618655, Cardiomyopathy, hypertrophic, 23, with or without LVNC MIM#612158, Cardiomyopathy, dilated, 1AA, with or without LVNC MIM#612158, Myopathy, congenital with structured cores and Z-line abnormalities MIM#618654
Mendeliome v1.3900 ABL1 Zornitza Stark reviewed gene: ABL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Human ABL1 Deficiency Syndrome (HADS); Mode of inheritance: None
Mendeliome v1.3900 ABL1 Zornitza Stark Phenotypes for gene: ABL1 were changed from Congenital heart defects and skeletal malformations syndrome MIM#617602 to Congenital heart defects and skeletal malformations syndrome MIM#617602; Human ABL1 Deficiency Syndrome (HADS)
Mendeliome v1.3899 ABL1 Zornitza Stark Publications for gene: ABL1 were set to PMID: 28288113; 30855488; 32643838
Mendeliome v1.3898 ABL1 Zornitza Stark Mode of inheritance for gene: ABL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3897 NSMF Zornitza Stark edited their review of gene: NSMF: Added comment: PMIDs 31220265, 34348883, 35316923, 39010903, 39809967 report 10 unrelated families with heterozygous NSMF missense or truncating variants linked to functional hypogonadotropic hypogonadism, congenital hypogonadotropic hypogonadism, Kallmann syndrome, normosmic isolated HH, delayed‑puberty HH, and adult‑onset azoospermia. Variants are mostly classified as VUS; most are present in gnomAD, some at implausibly high frequencies; no functional assays or robust segregation data are provided. Therefore retain Red rating.; Changed publications: 39809967, 39010903, 35316923, 34348883, 31220265; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.3897 DUSP6 Zornitza Stark Publications for gene: DUSP6 were set to 23643382
Mendeliome v1.3896 DUSP6 Zornitza Stark reviewed gene: DUSP6: Rating: RED; Mode of pathogenicity: None; Publications: 39809967, 37108593, 33819414; Phenotypes: Hypogonadotropic hypogonadism 19 with or without anosmia - MIM#615269; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.3896 DIAPH3 Zornitza Stark Classified gene: DIAPH3 as Amber List (moderate evidence)
Mendeliome v1.3896 DIAPH3 Zornitza Stark Gene: diaph3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3895 DIAPH3 Zornitza Stark edited their review of gene: DIAPH3: Changed rating: AMBER
Mendeliome v1.3895 DIAPH3 Zornitza Stark edited their review of gene: DIAPH3: Added comment: PMIDs 38860500 and 39767564: two further individuals reported, with different variant types (missense and frameshift) but little supporting evidence.; Changed publications: 23441200, 20624953, 38860500, 39767564
Mendeliome v1.3895 SELENOI Zornitza Stark changed review comment from: PMID 39806532: fourth family reported.; to: PMID 33454747: fourth family reported.
Mendeliome v1.3895 SELENOI Zornitza Stark Deleted their comment
Mendeliome v1.3895 SELENOI Zornitza Stark edited their review of gene: SELENOI: Added comment: Fourth family reported.; Changed publications: 33454747
Mendeliome v1.3895 SELENOI Zornitza Stark Phenotypes for gene: SELENOI were changed from developmental delay; spasticity; periventricular white mater abnormalities; peripheral neuropathy; seizures; bifid uvula in some affected individuals; microcephaly to Spastic paraplegia 81, autosomal recessive, MIM# 618768
Mendeliome v1.3894 SELENOI Zornitza Stark Publications for gene: SELENOI were set to 28052917; 39806532; 29500230
Mendeliome v1.3893 SELENOI Zornitza Stark Classified gene: SELENOI as Green List (high evidence)
Mendeliome v1.3893 SELENOI Zornitza Stark Gene: selenoi has been classified as Green List (High Evidence).
Mendeliome v1.3892 SELENOI Zornitza Stark edited their review of gene: SELENOI: Added comment: PMID 39806532: fourth family reported.; Changed rating: GREEN; Changed publications: 28052917, 29500230, 39806532, 33454747; Changed phenotypes: Spastic paraplegia 81, autosomal recessive, MIM# 618768
Mendeliome v1.3892 SELENOI Zornitza Stark Publications for gene: SELENOI were set to 28052917
Mendeliome v1.3891 SELENOI Zornitza Stark edited their review of gene: SELENOI: Added comment: PMIDs 29500230 and 39806532 add 2 additional unrelated families (bringing the total to 3 families) with autosomal recessive loss-of-function SELENOI variants causing complicated hereditary spastic paraplegia. Core features include early‑onset spastic paraplegia, white matter abnormalities, intellectual disability, sensorineural deafness, blindness, seizures, microcephaly, bifid uvula/cleft palate, and retinal pigment abnormalities. Some functional data.; Changed publications: 39806532, 29500230, 28052917; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SELENOI-related
Mendeliome v1.3891 GHSR Zornitza Stark Classified gene: GHSR as Green List (high evidence)
Mendeliome v1.3891 GHSR Zornitza Stark Gene: ghsr has been classified as Green List (High Evidence).
Mendeliome v1.3890 GHSR Zornitza Stark edited their review of gene: GHSR: Added comment: PMIDs 39785833 adds 24 unrelated families (25 individuals) with heterozygous loss‑of‑function GHSR variants and in‑vitro functional validation and short stature; PMIDs 37443653, 38838658, 37019085, 30753492, 36714562 contain additional families (singletons) with heterozygous or homozygous variants and detailed clinical data.; Changed rating: GREEN; Changed publications: 39785833, 25557026, 37443653, 38838658, 37019085, 30753492, 36714562
Mendeliome v1.3890 COA5 Zornitza Stark Publications for gene: COA5 were set to 21457908
Mendeliome v1.3889 COA5 Zornitza Stark edited their review of gene: COA5: Added comment: Second family reported but same homozygous missense variant.; Changed publications: 21457908, 36641477
Mendeliome v1.3889 TPCN2 Zornitza Stark Publications for gene: TPCN2 were set to 20197744; 26918892
Mendeliome v1.3888 TPCN2 Zornitza Stark Mode of inheritance for gene: TPCN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3887 TPCN2 Zornitza Stark Classified gene: TPCN2 as Amber List (moderate evidence)
Mendeliome v1.3887 TPCN2 Zornitza Stark Gene: tpcn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3886 TRMT1L Zornitza Stark Marked gene: TRMT1L as ready
Mendeliome v1.3886 TRMT1L Zornitza Stark Gene: trmt1l has been classified as Red List (Low Evidence).
Mendeliome v1.3886 TRMT1L Zornitza Stark gene: TRMT1L was added
gene: TRMT1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRMT1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT1L were set to 39786990
Phenotypes for gene: TRMT1L were set to Neurodevelopmental disorder, MONDO:0700092, TRMT1L-related
Review for gene: TRMT1L was set to RED
Added comment: PMID 39786990 reports 2 individuals from a single family with an autosomal recessive homozygous missense variant c.1535C>T (p.Pro512Leu) presenting with early‑onset neurodegenerative syndrome (distal motor neuropathy, leukodystrophy, intellectual disability, hypotonia, contractures). Functional assays in patient fibroblasts show reduced acp3U tRNA modification that is rescued by wild‑type TRMT1L expression.
Sources: Literature
Mendeliome v1.3885 SORCS2 Zornitza Stark Marked gene: SORCS2 as ready
Mendeliome v1.3885 SORCS2 Zornitza Stark Gene: sorcs2 has been classified as Red List (Low Evidence).
Mendeliome v1.3885 SORCS2 Zornitza Stark gene: SORCS2 was added
gene: SORCS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SORCS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SORCS2 were set to 39810752
Phenotypes for gene: SORCS2 were set to Neurodevelopmental disorder, MONDO:0700092, SORCS2-related
Review for gene: SORCS2 was set to RED
Added comment: PMID 39810752 reports one individual with a de novo heterozygous missense SORCS2 variant (c.2614C>T, p.Pro872Ser) presenting with neonatal encephalopathy and refractory seizures. Cell‑based assays demonstrate disrupted SorCS2 dimerization and mislocalization, supporting a loss‑of‑function mechanism. Variant is absent from gnomAD.
Sources: Literature
Mendeliome v1.3884 RNU6-9 Zornitza Stark Marked gene: RNU6-9 as ready
Mendeliome v1.3884 RNU6-9 Zornitza Stark Gene: rnu6-9 has been classified as Green List (High Evidence).
Mendeliome v1.3884 RNU6-9 Zornitza Stark Classified gene: RNU6-9 as Green List (high evidence)
Mendeliome v1.3884 RNU6-9 Zornitza Stark Gene: rnu6-9 has been classified as Green List (High Evidence).
Mendeliome v1.3883 RNU6-9 Zornitza Stark gene: RNU6-9 was added
gene: RNU6-9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU6-9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RNU6-9 were set to 39830270
Phenotypes for gene: RNU6-9 were set to retinitis pigmentosa MONDO:0019200, RNU6-9-related
Review for gene: RNU6-9 was set to GREEN
Added comment: PMID 39830270 reports 99 individuals with autosomal dominant retinitis pigmentosa, adolescent onset, progressive visual field loss, caused by de novo and inherited insertion variants n.55_56insG and n.56_57insG in RNU6-9. The variants act via a dominant‑negative mechanism and co‑immunoprecipitation in HeLa cells shows increased binding to SART3 and PRPF31. Note multiple RNU6 paralogues.
Sources: Literature
Mendeliome v1.3882 RNU6-8 Zornitza Stark Marked gene: RNU6-8 as ready
Mendeliome v1.3882 RNU6-8 Zornitza Stark Gene: rnu6-8 has been classified as Green List (High Evidence).
Mendeliome v1.3882 RNU6-8 Zornitza Stark Classified gene: RNU6-8 as Green List (high evidence)
Mendeliome v1.3882 RNU6-8 Zornitza Stark Gene: rnu6-8 has been classified as Green List (High Evidence).
Mendeliome v1.3881 RNU6-8 Zornitza Stark gene: RNU6-8 was added
gene: RNU6-8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU6-8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RNU6-8 were set to 39830270
Phenotypes for gene: RNU6-8 were set to Retinitis pigmentosa MONDO:0019200, RNU6-8-related
Review for gene: RNU6-8 was set to GREEN
Added comment: PMID 39830270 reports multiple individuals with a dominant insertion variant (n.55_56insG) in RNU6-8 presenting with autosomal dominant retinitis pigmentosa, adolescent onset and progressive peripheral vision loss. Co‑IP assays demonstrate increased binding of mutant U6 snRNA to SART3 and PRPF31, supporting a dominant‑negative mechanism; both de novo and inherited cases are described. Note multiple RNU6 paralogues.
Sources: Literature
Mendeliome v1.3880 RNU6-2 Zornitza Stark Marked gene: RNU6-2 as ready
Mendeliome v1.3880 RNU6-2 Zornitza Stark Gene: rnu6-2 has been classified as Green List (High Evidence).
Mendeliome v1.3880 RNU6-2 Zornitza Stark Classified gene: RNU6-2 as Green List (high evidence)
Mendeliome v1.3880 RNU6-2 Zornitza Stark Gene: rnu6-2 has been classified as Green List (High Evidence).
Mendeliome v1.3879 RNU6-2 Zornitza Stark gene: RNU6-2 was added
gene: RNU6-2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU6-2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RNU6-2 were set to 39830270
Phenotypes for gene: RNU6-2 were set to Retinitis pigmentosa MONDO:0019200, RNU6-2-related
Review for gene: RNU6-2 was set to GREEN
Added comment: PMID 39830270 reports 99 individuals with autosomal dominant retinitis pigmentosa, adolescent onset and progressive peripheral vision loss. Insertion variants n.55_56insG and n.56_57insG in the U6 snRNA were identified, with de novo events in several cases and inherited segregation in others. Co‑IP assays demonstrate increased binding of mutant U6 to di‑snRNP proteins, indicating a dominant‑negative gain‑of‑function effect on spliceosomal assembly.
Sources: Literature
Mendeliome v1.3878 RNU6-1 Zornitza Stark Marked gene: RNU6-1 as ready
Mendeliome v1.3878 RNU6-1 Zornitza Stark Gene: rnu6-1 has been classified as Green List (High Evidence).
Mendeliome v1.3878 RNU6-1 Zornitza Stark Classified gene: RNU6-1 as Green List (high evidence)
Mendeliome v1.3878 RNU6-1 Zornitza Stark Gene: rnu6-1 has been classified as Green List (High Evidence).
Mendeliome v1.3877 RNU6-1 Zornitza Stark gene: RNU6-1 was added
gene: RNU6-1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU6-1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RNU6-1 were set to 39830270
Phenotypes for gene: RNU6-1 were set to retinitis pigmentosa MONDO:0019200, RNU6-1-related
Review for gene: RNU6-1 was set to GREEN
Added comment: RNU6-1 encodes the U6 small nuclear RNA, a core spliceosomal component involved in pre-mRNA splicing. PMID 39830270 reports 99 individuals with autosomal dominant adolescent-onset progressive retinitis pigmentosa caused by heterozygous insertion variants (n.55_56insG and n.56_57insG). The disease follows a dominant inheritance pattern with de novo events confirmed in seven individuals, and functional assays demonstrate a dominant‑negative effect via increased binding of mutant U6 snRNA to SART3 and PRPF31.

Preprint.
Sources: Literature
Mendeliome v1.3876 FAM58A Zornitza Stark Marked gene: FAM58A as ready
Mendeliome v1.3876 FAM58A Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is CCNQ
Mendeliome v1.3876 FAM58A Zornitza Stark Gene: fam58a has been classified as Green List (High Evidence).
Mendeliome v1.3876 FAM58A Zornitza Stark Tag new gene name tag was added to gene: FAM58A.
Mendeliome v1.3876 OTP Zornitza Stark Marked gene: OTP as ready
Mendeliome v1.3876 OTP Zornitza Stark Gene: otp has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3876 OTP Zornitza Stark Classified gene: OTP as Amber List (moderate evidence)
Mendeliome v1.3876 OTP Zornitza Stark Gene: otp has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3875 OTP Zornitza Stark gene: OTP was added
gene: OTP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OTP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: OTP were set to 39813316; 29107289
Phenotypes for gene: OTP were set to Obesity disorder, MONDO:0011122, OTP-related
Review for gene: OTP was set to AMBER
Added comment: PMID 29107289 reports a single individual with a heterozygous missense OTP variant (p.Q153R) presenting with severe early‑onset obesity and attention‑deficit disorder. PMID 39813316 adds five unrelated individuals carrying predicted loss‑of‑function OTP variants and confirms the Q153R case, together implicating heterozygous loss‑of‑function OTP as a cause of early‑onset severe obesity with metabolic comorbidities (type 2 diabetes, dyslipidemia, hepatic steatosis). However, individuals are ascertained from UK Biobank, hence clinical details are sparse. Mouse models with OTP haploinsufficiency or a Q153R knock‑in recapitulate hyperphagia and obesity, providing functional support.
Sources: Literature
Mendeliome v1.3874 NKAPL Zornitza Stark Marked gene: NKAPL as ready
Mendeliome v1.3874 NKAPL Zornitza Stark Gene: nkapl has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3874 NKAPL Zornitza Stark Classified gene: NKAPL as Amber List (moderate evidence)
Mendeliome v1.3874 NKAPL Zornitza Stark Gene: nkapl has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3873 NKAPL Zornitza Stark gene: NKAPL was added
gene: NKAPL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NKAPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NKAPL were set to 39824811
Phenotypes for gene: NKAPL were set to Spermatogenic failure, MONDO:0004983, NKAPL-related
Review for gene: NKAPL was set to AMBER
Added comment: PMID 39824811 reports four unrelated Han Chinese men with heterozygous NKAPL variants (c.844G>A, c.896C>G, c.1040G>A and c.1046_1047delTG) presenting with non‑obstructive azoospermia. Supportive mouse model. However, note 3 of the 4 variants are present at relatively high frequencies in gnomAD.
Sources: Literature
Mendeliome v1.3872 TDRD6 Zornitza Stark Marked gene: TDRD6 as ready
Mendeliome v1.3872 TDRD6 Zornitza Stark Gene: tdrd6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3872 TDRD6 Zornitza Stark Classified gene: TDRD6 as Amber List (moderate evidence)
Mendeliome v1.3872 TDRD6 Zornitza Stark Gene: tdrd6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3871 TDRD6 Zornitza Stark gene: TDRD6 was added
gene: TDRD6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TDRD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDRD6 were set to 39764564; 39331689
Phenotypes for gene: TDRD6 were set to Infertility disorder, MONDO:0005047, TDRD6-related
Review for gene: TDRD6 was set to AMBER
Added comment: PMID 39331689 reports one family and PMID 39764564 reports two families, together three unrelated families with biallelic variants in TDRD6 causing severe oligo‑astheno‑teratozoospermia (OAT) and early embryonic arrest after ICSI. Supportive animal model. Note missense variant is relatively common on gnomAD.
Sources: Literature
Mendeliome v1.3870 SPAG9 Zornitza Stark Marked gene: SPAG9 as ready
Mendeliome v1.3870 SPAG9 Zornitza Stark Gene: spag9 has been classified as Red List (Low Evidence).
Mendeliome v1.3870 SPAG9 Zornitza Stark gene: SPAG9 was added
gene: SPAG9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPAG9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPAG9 were set to 39846792
Phenotypes for gene: SPAG9 were set to Neurodevelopmental disorder, MONDO:0700092, SPAG9-related
Review for gene: SPAG9 was set to RED
Added comment: PMID 39846792 reports 2 individuals from 2 families with the same biallelic loss-of-function frameshift variant in SPAG9 presenting with coarse facial features, albinism, cataract, skeletal abnormalities and severe developmental delay. Limited functional data, possible founder variant.
Sources: Literature
Mendeliome v1.3869 PBXIP1 Zornitza Stark Marked gene: PBXIP1 as ready
Mendeliome v1.3869 PBXIP1 Zornitza Stark Gene: pbxip1 has been classified as Red List (Low Evidence).
Mendeliome v1.3869 PBXIP1 Zornitza Stark gene: PBXIP1 was added
gene: PBXIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PBXIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PBXIP1 were set to 39786576; 38947059
Phenotypes for gene: PBXIP1 were set to non-syndromic genetic hearing loss, MONDO:0019497, PBXIP1-related
Review for gene: PBXIP1 was set to RED
Added comment: One individual from a consanguineous family with a homozygous nonsense PBXIP1 variant (c.1722G>A; p.Trp574*) causing bilateral cochlear aplasia and congenital profound sensorineural hearing loss. Functional studies using iPSC‑derived organoids with knockout and knock‑in of the nonsense allele recapitulate the human phenotype, supporting a loss‑of‑function disease mechanism.
Sources: Literature
Mendeliome v1.3868 NUBP2 Zornitza Stark Marked gene: NUBP2 as ready
Mendeliome v1.3868 NUBP2 Zornitza Stark Gene: nubp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3868 NUBP2 Zornitza Stark Classified gene: NUBP2 as Amber List (moderate evidence)
Mendeliome v1.3868 NUBP2 Zornitza Stark Gene: nubp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3867 NUBP2 Zornitza Stark gene: NUBP2 was added
gene: NUBP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUBP2 were set to 39867373
Phenotypes for gene: NUBP2 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: NUBP2 was set to AMBER
Added comment: PMID 39867373 reports 2 individuals from 2 unrelated families with biallelic missense variants in NUBP2 presenting with congenital primary microcephaly, intrauterine growth restriction, severe joint contractures and facial dysmorphism. A forebrain‑specific conditional Nubp2 knockout mouse recapitulates the severe microcephaly, and rescue assays show patient alleles fail to restore growth, supporting a loss‑of‑function mechanism.

Preprint.
Sources: Literature
Mendeliome v1.3866 IQUB Zornitza Stark Marked gene: IQUB as ready
Mendeliome v1.3866 IQUB Zornitza Stark Gene: iqub has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3866 IQUB Zornitza Stark Classified gene: IQUB as Amber List (moderate evidence)
Mendeliome v1.3866 IQUB Zornitza Stark Gene: iqub has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3865 IQUB Zornitza Stark gene: IQUB was added
gene: IQUB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQUB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQUB were set to 39849482; 36355624
Phenotypes for gene: IQUB were set to Spermatogenic failure, MONDO:0004983, IQUB-related
Review for gene: IQUB was set to AMBER
Added comment: PMID 36355624 and PMID 39849482 report 2 unrelated families with autosomal recessive loss‑of‑function variants in IQUB (c.942T>G p.Tyr314* and c.842del p.L281Pfs*28) causing male infertility due to severe asthenospermia/astenozoospermia with normal sperm morphology. Functional studies include mouse knockout/knock‑in models that recapitulate the infertility phenotype.
Sources: Literature
Mendeliome v1.3864 GCC2 Zornitza Stark Marked gene: GCC2 as ready
Mendeliome v1.3864 GCC2 Zornitza Stark Gene: gcc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3864 GCC2 Zornitza Stark Classified gene: GCC2 as Amber List (moderate evidence)
Mendeliome v1.3864 GCC2 Zornitza Stark Gene: gcc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3863 GCC2 Zornitza Stark gene: GCC2 was added
gene: GCC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCC2 were set to 39813120
Phenotypes for gene: GCC2 were set to Inborn error of immunity, MONDO:0003778, GCC2-related
Review for gene: GCC2 was set to AMBER
Added comment: PMID 39813120 reports two individuals from two families with compound het missense GCC2 variants presenting with natural killer cell deficiency, recurrent viral infections, and impaired lytic granule convergence. Functional assays show markedly reduced NK cell cytotoxicity and defective granule convergence, which is rescued by wild‑type GCC2 but not by the E1608G mutant.
Sources: Literature
Mendeliome v1.3862 EXD3 Zornitza Stark Marked gene: EXD3 as ready
Mendeliome v1.3862 EXD3 Zornitza Stark Gene: exd3 has been classified as Red List (Low Evidence).
Mendeliome v1.3862 EXD3 Zornitza Stark gene: EXD3 was added
gene: EXD3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXD3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EXD3 were set to 37396523
Phenotypes for gene: EXD3 were set to Cataract, MONDO:0005129, EXD3-related
Review for gene: EXD3 was set to RED
Added comment: PMID 37396523 reports 34 individuals from 3 unrelated families where a heterozygous missense variant c.112C>T (p.Arg38Trp) segregated in an autosomal dominant manner, presenting with bilateral posterior polar congenital cataract. No functional data. Variant is present in gnomAD in 13 individuals. Haplotype analysis suggested it had arisen independently.
Sources: Literature
Mendeliome v1.3861 EP400 Zornitza Stark reviewed gene: EP400: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3861 LETM1 Zornitza Stark edited their review of gene: LETM1: Changed publications: 36055214
Mendeliome v1.3861 LETM1 Zornitza Stark commented on gene: LETM1: The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%).
Mendeliome v1.3861 PEX11B Zornitza Stark Publications for gene: PEX11B were set to 20301621; 22581968
Mendeliome v1.3860 PEX11B Zornitza Stark edited their review of gene: PEX11B: Added comment: Additional families reported.; Changed rating: GREEN; Changed publications: 38423277, 31724321, 28129423; Changed phenotypes: Peroxisome biogenesis disorder 14B - MIM#614920; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3860 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from Coloboma of optic nerve - MIM# 120430; Coloboma, ocular - MIM#120200; Morning glory disc anomaly - MIM#120430; Aniridia - MIM#106210; Anterior segment dysgenesis 5, multiple subtypes - MIM#604229; Cataract with late-onset corneal dystrophy - MIM#106210; Foveal hypoplasia 1- MIM#136520; Keratitis - MIM#148190; Optic nerve hypoplasia - MIM#165550 to PAX6-related ocular dysgenesis MONDO:0800183
Mendeliome v1.3859 PAX6 Zornitza Stark reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PAX6-related ocular dysgenesis MONDO:0800183; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3859 MAF Zornitza Stark Phenotypes for gene: MAF were changed from Ayme-Gripp syndrome (MIM#601088) to Cataract 21, multiple types, MIM# 610202; Ayme-Gripp syndrome, MIM# 601088
Mendeliome v1.3858 MAF Zornitza Stark Publications for gene: MAF were set to 30160832; 34643041
Mendeliome v1.3857 Zornitza Stark Added reviews for gene MAF from panel Cataract
Mendeliome v1.3856 INPP5K Zornitza Stark Tag founder tag was added to gene: INPP5K.
Mendeliome v1.3856 HCN2 Zornitza Stark Publications for gene: HCN2 were set to 22131395; 30986657; 29064616; 20437590; 12514127; 17931874
Mendeliome v1.3855 HCN2 Zornitza Stark edited their review of gene: HCN2: Added comment: PMID 40468825 reports 21 individuals with HCN2 variants from 15 unrelated families. The phenotypic spectrum included developmental delay/intellectual disability (DD/ID, 17/21), epilepsy (10/21), language disorders (16/21), movement disorders (12/21), and axial hypotonia (10/21). Thirteen pathogenic variants (12 new and 1 already described) were identified: 11 missense (8 monoallelic and 3 biallelic), 1 recurrent inframe deletion (monoallelic), and 1 frameshift (biallelic). Functional analysis of p.(Arg324His) variant showed a strong increase of HCN2 conductance, whereas p.(Ala363Val) and p.(Met374Leu) exhibited dominant negative effects. The p.(Leu377His), p.(Pro493Leu), and p.(Gly587Asp) variants rendered HCN2 electrophysiologically silent and impaired membrane trafficking. Structural 3D-analysis revealed that, except for p.(Arg324His), all variants altered HCN2 stability.; Changed publications: 22131395, 30986657, 29064616, 20437590, 12514127, 17931874, 40468825
Mendeliome v1.3855 BICC1 Chirag Patel Publications for gene: BICC1 were set to 21922595, 35005812, 39253489, 39655693, 41278337
Mendeliome v1.3855 BICC1 Chirag Patel Publications for gene: BICC1 were set to 21922595, 35005812, 39253489, 39655693, 41278337
Mendeliome v1.3855 BICC1 Chirag Patel Publications for gene: BICC1 were set to 21922595, 35005812, 39253489, 39655693, 41278337
Mendeliome v1.3855 BICC1 Chirag Patel Publications for gene: BICC1 were set to 21922595, 35005812, 39253489, 39655693, 41278337
Mendeliome v1.3855 BICC1 Chirag Patel Publications for gene: BICC1 were set to 21922595, 35005812, 39253489, 39655693, 41278337
Mendeliome v1.3855 BICC1 Chirag Patel Publications for gene: BICC1 were set to 21922595, 35005812, 39253489, 39655693, 41278337
Mendeliome v1.3854 BICC1 Chirag Patel Publications for gene: BICC1 were set to 21922595
Mendeliome v1.3853 BICC1 Chirag Patel Phenotypes for gene: BICC1 were changed from Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642 to Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642
Mendeliome v1.3853 BICC1 Chirag Patel Phenotypes for gene: BICC1 were changed from Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642 to Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642
Mendeliome v1.3852 BICC1 Chirag Patel Phenotypes for gene: BICC1 were changed from Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642 to Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642
Mendeliome v1.3852 BICC1 Chirag Patel Phenotypes for gene: BICC1 were changed from Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642 to Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642
Mendeliome v1.3852 BICC1 Chirag Patel Phenotypes for gene: BICC1 were changed from Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642 to Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642
Mendeliome v1.3852 BICC1 Chirag Patel Phenotypes for gene: BICC1 were changed from Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642 to Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642
Mendeliome v1.3852 BICC1 Chirag Patel Phenotypes for gene: BICC1 were changed from {Renal dysplasia, cystic, susceptibility to}; OMIM #601331 to Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642
Mendeliome v1.3851 BICC1 Chirag Patel Mode of inheritance for gene: BICC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3850 BICC1 Chirag Patel Classified gene: BICC1 as Amber List (moderate evidence)
Mendeliome v1.3850 BICC1 Chirag Patel Gene: bicc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3849 Chirag Patel Added reviews for gene BICC1 from panel Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic
Mendeliome v1.3848 RPS28 Zornitza Stark Phenotypes for gene: RPS28 were changed from Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164 to Diamond Blackfan anaemia 15 with mandibulofacial dysostosis, MIM# 606164
Mendeliome v1.3847 RPS28 Zornitza Stark Publications for gene: RPS28 were set to 24942156
Mendeliome v1.3846 RPS28 Zornitza Stark Classified gene: RPS28 as Green List (high evidence)
Mendeliome v1.3846 RPS28 Zornitza Stark Gene: rps28 has been classified as Green List (High Evidence).
Mendeliome v1.3845 RPS28 Zornitza Stark edited their review of gene: RPS28: Added comment: PMID 40135709 reports a new individual with a heterozygous de novo start‑codon loss‑of‑function variant (c.2T>C) causing Diamond‑Blackfan anaemia and Pierre Robin sequence; Changed rating: GREEN; Changed publications: 24942156, 40135709; Changed phenotypes: Diamond Blackfan anaemia 15 with mandibulofacial dysostosis, MIM# 606164
Mendeliome v1.3845 DNAJA3 Zornitza Stark Publications for gene: DNAJA3 were set to 34750646; 30770860
Mendeliome v1.3844 DNAJA3 Zornitza Stark edited their review of gene: DNAJA3: Added comment: PMID 41354729 describes a third unrelated family with compound heterozygous DNAJA3 missense variants presenting with isolated recurrent polyneuropathy. Retain Amber rating as the genetic and functional data are both limited.; Changed publications: 34750646, 30770860, 41354729
Mendeliome v1.3844 TMEM72 Zornitza Stark Marked gene: TMEM72 as ready
Mendeliome v1.3844 TMEM72 Zornitza Stark Gene: tmem72 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3844 TMEM72 Zornitza Stark Classified gene: TMEM72 as Amber List (moderate evidence)
Mendeliome v1.3844 TMEM72 Zornitza Stark Gene: tmem72 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3843 TMEM72 Zornitza Stark gene: TMEM72 was added
gene: TMEM72 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM72 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM72 were set to 41308066
Phenotypes for gene: TMEM72 were set to Nephronophthisis, MONDO:0019005, TMEM72-related
Review for gene: TMEM72 was set to AMBER
Added comment: PMID 41308066 reports nine individuals from six families with biallelic TMEM72 variants. However, families A-C share same variant and haplotype, suggestive of a found effect. Further, the variant is p.Gln2*, which likely escapes NMD. Clinical presentation was nephronophthisis‑like kidney disease with adult‑onset kidney failure, hypertension and polyuria. One family (F) had homozygous missense variant, p.Gly124Ser, and showed prenatal‑onset cystic kidney disease, vesicoureteral reflux and early epilepsy. Functional studies demonstrate reduced TMEM72 expression and ciliary localisation.

Concerns about the quality of the genetic and experimental data, hence Amber rating.
Sources: Literature
Mendeliome v1.3842 PPP1R3F Zornitza Stark Classified gene: PPP1R3F as Amber List (moderate evidence)
Mendeliome v1.3842 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3841 LRP6 Zornitza Stark Phenotypes for gene: LRP6 were changed from Tooth agenesis, selective, 7, MIM# 616724; Exudative vitreoretinopathy 8, MIM# 621268 to Osteopetrosis, autosomal dominant 4, MIM# 621449; Tooth agenesis, selective, 7, MIM# 616724; Exudative vitreoretinopathy 8, MIM# 621268
Mendeliome v1.3840 LRP6 Zornitza Stark Publications for gene: LRP6 were set to 26387593; 34896607
Mendeliome v1.3839 LRP6 Zornitza Stark changed review comment from: 8 individuals from 3 unrelated families reported, all with missense variants. Insufficient segregation evidence in two of the families. Supportive mouse model.; to: Association with vitreoretinopathy: 8 individuals from 3 unrelated families reported, all with missense variants. Insufficient segregation evidence in two of the families. Supportive mouse model. AMBER for this association.
Mendeliome v1.3839 LRP6 Zornitza Stark edited their review of gene: LRP6: Added comment: Association with osteopetrosis: 5 families reported with a dentoosseous disorder characterised by enhanced osteoblast-mediated bone formation resulting in generalized osteosclerosis and endosteal hyperostosis. Other features include missing teeth, torus palatinus, and intraoral exostoses that sometimes surround teeth. GREEN for this association.; Changed rating: GREEN; Changed publications: 34896607, 31085352, 32730923, 37065631, 38385987; Changed phenotypes: Exudative vitreoretinopathy 8, MIM# 621268, Osteopetrosis, autosomal dominant 4, MIM# 621449
Mendeliome v1.3839 RRP12 Zornitza Stark Phenotypes for gene: RRP12 were changed from Syndromic disease, MONDO:0002254, RRP12-related; Brain calcifications to Basal ganglia calcification, idiopathic, 11, autosomal recessive, MIM# 621452
Mendeliome v1.3838 RRP12 Zornitza Stark reviewed gene: RRP12: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 11, autosomal recessive, MIM# 621452; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3838 USP25 Zornitza Stark Tag disputed tag was added to gene: USP25.
Mendeliome v1.3838 USP25 Zornitza Stark Classified gene: USP25 as Red List (low evidence)
Mendeliome v1.3838 USP25 Zornitza Stark Gene: usp25 has been classified as Red List (Low Evidence).
Mendeliome v1.3837 USP25 Zornitza Stark reviewed gene: USP25: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3837 PPP1R3F Paul De Fazio reviewed gene: PPP1R3F: Rating: AMBER; Mode of pathogenicity: None; Publications: 37531237; Phenotypes: Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v1.3837 MARCHF6_FAME3_TTTCA Bryony Thompson MARCH6_FAME3_TTTCA was changed to MARCHF6_FAME3_TTTCA
Mendeliome v1.3836 Bryony Thompson Copied STR MARCH6_FAME3_TTTCA from panel Genetic Epilepsy
Mendeliome v1.3836 MARCH6_FAME3_TTTCA Bryony Thompson STR: MARCH6_FAME3_TTTCA was added
STR: MARCH6_FAME3_TTTCA was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for STR: MARCH6_FAME3_TTTCA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: MARCH6_FAME3_TTTCA were set to 31664039
Phenotypes for STR: MARCH6_FAME3_TTTCA were set to Epilepsy, familial adult myoclonic, 3 MIM#613608
Mendeliome v1.3835 BAZ2B Zornitza Stark Publications for gene: BAZ2B were set to 31999386; 28135719; 25363768
Mendeliome v1.3834 LAMP3 Zornitza Stark Marked gene: LAMP3 as ready
Mendeliome v1.3834 LAMP3 Zornitza Stark Gene: lamp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3834 Zornitza Stark Copied gene LAMP3 from panel Pulmonary Fibrosis_Interstitial Lung Disease
Mendeliome v1.3834 LAMP3 Zornitza Stark gene: LAMP3 was added
gene: LAMP3 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: LAMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMP3 were set to 40023045; 34161347
Phenotypes for gene: LAMP3 were set to Interstitial lung disease, MONDO:0015925, LAMP3-related
Mendeliome v1.3833 BAZ2B Sarah Milton edited their review of gene: BAZ2B: Added comment: Reviewed new literature in regards to gene disease association.

Classified as limited by ClinGen in 2022. Additional publication Sewani et al 2024 describes 10 additional individuals with variants in BAZ2B however a number were inherited, some were multigenic CNV's.

No functional evidence/animal models to support haploinsufficiency/loss of function as resulting in neurodev phenotype have been published thus far.

To remain as amber given a number of inherited variants, lack of functional evidence and LOF variants present in gnomAD.; Changed rating: AMBER; Changed publications: PMID: 37872713; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3833 KIF26B Lucy Spencer Phenotypes for gene: KIF26B were changed from Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis to Multiple congenital anomalies MONDO:0019042, KIF26B-related
Mendeliome v1.3832 KIF21B Lucy Spencer Phenotypes for gene: KIF21B were changed from Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly to Neurodevelopmental disorder MONDO:0700092, KIF21B-related
Mendeliome v1.3831 KIF21A Rylee Peters Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700 to Fibrosis of extraocular muscles, congenital, 1/3B, MIM#135700; Arthrogryposis multiplex congenita, MONDO:0015168, KIF21A-related
Mendeliome v1.3830 KIF21A Rylee Peters Publications for gene: KIF21A were set to 15621876; 15223798; 15621877; 18332320; 28930843; 27513105; 26190014; 24656932
Mendeliome v1.3829 KIF21A Rylee Peters Mode of inheritance for gene: KIF21A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3828 KIF21A Rylee Peters reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37921537, 39643435, 41282472, 32141982, 24715754, 36494820, 22699964, 34740919, 32686171; Phenotypes: Fibrosis of extraocular muscles, congenital, 1/3B, MIM#135700, Arthrogryposis multiplex congenita, MONDO:0015168, KIF21A-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3828 KIF17 Lucy Spencer Phenotypes for gene: KIF17 were changed from Microphthalmia; Coloboma to Microphthalmia, isolated, with coloboma MONDO:0000170, KIF17-related
Mendeliome v1.3827 KIAA1217 Lucy Spencer Phenotypes for gene: KIAA1217 were changed from Vertebral anomalies, syndromic and non-syndromic to Skeletal system disorder MONDO:0005172, KIAA1217-related
Mendeliome v1.3826 KHDRBS1 Lucy Spencer Phenotypes for gene: KHDRBS1 were changed from Premature ovarian failure to Premature ovarian failure MONDO:0005387, KHDRBS1-related
Mendeliome v1.3825 KDM7A Lucy Spencer Phenotypes for gene: KDM7A were changed from Cerebral palsy to Cerebral palsy MONDO:0006497, KDM7A-related
Mendeliome v1.3824 KCTD3 Lucy Spencer Phenotypes for gene: KCTD3 were changed from Epilepsy; Intellectual disability; Posterior fossa abnormalities to Neurodevelopmental disorder MONDO:0700092, KCTD3-related
Mendeliome v1.3823 KCNT1 Lucy Spencer Phenotypes for gene: KCNT1 were changed from Epilepsy, nocturnal frontal lobe, 5, MIM# 615005; Epileptic encephalopathy, early infantile, 14, MIM# 614959 to Epilepsy, nocturnal frontal lobe, 5, MIM# 615005; Developmental and epileptic encephalopathy 14 MIM# 614959
Mendeliome v1.3822 KCNQ2 Lucy Spencer Phenotypes for gene: KCNQ2 were changed from Epileptic encephalopathy, early infantile, 7, 613720; Seizures, benign neonatal, 1, 121200; Myokymia, 121200 to Developmental and epileptic encephalopathy 7 MIM#613720; Seizures, benign neonatal, 1, MIM#121200; Myokymia, MIM#121200
Mendeliome v1.3821 KCNMA1 Lucy Spencer reviewed gene: KCNMA1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Generalized epilepsy-paroxysmal dyskinesia syndrome MONDO:0012276; Mode of inheritance: None
Mendeliome v1.3821 KCNMA1 Lucy Spencer Phenotypes for gene: KCNMA1 were changed from Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446; Cerebellar atrophy, developmental delay, and seizures, MIM# 617643; Liang-Wang syndrome, MIM# 618729 to Generalized epilepsy-paroxysmal dyskinesia syndrome MONDO:0012276; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446; Cerebellar atrophy, developmental delay, and seizures, MIM# 617643; Liang-Wang syndrome, MIM# 618729
Mendeliome v1.3820 KCNJ8 Lucy Spencer Phenotypes for gene: KCNJ8 were changed from Cantú Syndrome to Brugada syndrome 1 MONDO:0011001, KCNJ8-related; Hypertrichotic osteochondrodysplasia Cantu type MONDO:0009406, KCNJ8-related
Mendeliome v1.3819 KCNH1 Lucy Spencer Phenotypes for gene: KCNH1 were changed from Temple-Baraitser syndrome, OMIM:611816; Zimmermann-Laband syndrome 1, OMIM:135500; Intellectual disability; Encephalopathy without features of TBS/ZLS to KCNH1 associated disorder MONDO:0100485; Temple-Baraitser syndrome, OMIM:611816; Zimmermann-Laband syndrome 1, OMIM:135500
Mendeliome v1.3818 KCNH1 Lucy Spencer reviewed gene: KCNH1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: KCNH1 associated disorder MONDO:0100485; Mode of inheritance: None
Mendeliome v1.3818 KCNE5 Lucy Spencer Phenotypes for gene: KCNE5 were changed from Atrial fibrillation; Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263, KCNE5-related; Atrial fibrillation MONDO:0004981, KCNE5-related
Mendeliome v1.3817 KCNE3 Lucy Spencer Phenotypes for gene: KCNE3 were changed from Brugada syndrome to Brugada syndrome 6 MIM#613119
Mendeliome v1.3816 KCND2 Lucy Spencer Phenotypes for gene: KCND2 were changed from Neurodevelopmental disorder MONDO:0700092; global developmental delay, HP:0001263; seizure, HP:0001250 to Neurodevelopmental disorder MONDO:0700092, KCND2-related
Mendeliome v1.3815 KATNAL2 Lucy Spencer Phenotypes for gene: KATNAL2 were changed from Oligo-astheno-teratozoospermia; Autism to Male infertility MONDO:0005372, KATNAL2-related; Complex neurodevelopmental disorder MONDO:0100038, KATNAL2-related
Mendeliome v1.3814 KATNAL2 Lucy Spencer commented on gene: KATNAL2
Mendeliome v1.3814 KANK4 Lucy Spencer Phenotypes for gene: KANK4 were changed from Nephrotic syndrome to Nephrotic syndrome MONDO:0005377, KANK4-related
Mendeliome v1.3813 KALRN Lucy Spencer Phenotypes for gene: KALRN were changed from Susceptibility to coronary heart disease; Intellectual disability to Coronary artery disorder MONDO:0005010, KALRN-related; Intellectual disability (MONDO:0001071), KALRN-related
Mendeliome v1.3812 JAM2 Lucy Spencer Phenotypes for gene: JAM2 were changed from Primary brain calcification to Basal ganglia calcification, idiopathic, 8, autosomal recessive MIM#618824
Mendeliome v1.3811 JAG1 Lucy Spencer Phenotypes for gene: JAG1 were changed from Alagille syndrome 1, MIM# 118450; Charcot-Marie-Tooth disease, axonal, type 2HH, MIM# 619574 to Alagille syndrome due to a JAG1 point mutation MONDO:0016862; Charcot-Marie-Tooth disease, axonal, type 2HH MIM#619574
Mendeliome v1.3810 JAG1 Lucy Spencer reviewed gene: JAG1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Alagille syndrome due to a JAG1 point mutation MONDO:0016862, Charcot-Marie-Tooth disease, axonal, type 2HH MIM#619574; Mode of inheritance: None
Mendeliome v1.3810 ITSN2 Lucy Spencer Phenotypes for gene: ITSN2 were changed from Nephrotic syndrome to Nephrotic syndrome MONDO:0005377, ITSN2-related
Mendeliome v1.3809 ITGB4 Lucy Spencer Publications for gene: ITGB4 were set to 11328943; 9670011; 33225458; 30079450; 29380424; 29198538; 28557647
Mendeliome v1.3808 ITGB4 Lucy Spencer changed review comment from: Updating OMIMs, 2 listed below are now attached to different genes. Both current OMIMs are recessive only; to: Updating OMIMs, 2 listed below are now attached to different genes. Both current OMIMs are recessive only

Dominant reports appear to be rare, PMID: 35822394, 26817667, 36813478
Mendeliome v1.3808 ITGB4 Lucy Spencer Phenotypes for gene: ITGB4 were changed from Epidermolysis bullosa of hands and feet, MIM# 131800; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650; Epidermolysis bullosa, junctional, with pyloric atresia, MIM# 226730 to Epidermolysis bullosa, junctional 5A, intermediate MIM#619816; Epidermolysis bullosa, junctional 5B, with pyloric atresia MIM#226730
Mendeliome v1.3807 ITGB4 Lucy Spencer reviewed gene: ITGB4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa, junctional 5A, intermediate MIM#619816, Epidermolysis bullosa, junctional 5B, with pyloric atresia MIM#226730; Mode of inheritance: None
Mendeliome v1.3807 ITFG2 Lucy Spencer Phenotypes for gene: ITFG2 were changed from Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia to Neurodevelopmental disorder (MONDO:0700092), ITFG2-related
Mendeliome v1.3806 ISPD Lucy Spencer Phenotypes for gene: ISPD were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052 to Myopathy caused by variation in CRPPA MONDO:0100530; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052
Mendeliome v1.3805 ISPD Lucy Spencer reviewed gene: ISPD: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy caused by variation in CRPPA MONDO:0100530; Mode of inheritance: None
Mendeliome v1.3805 ISLR2 Lucy Spencer Phenotypes for gene: ISLR2 were changed from hydrocephalus; arthrogryposis; abdominal distension to Multiple congenital anomalies MONDO:0019042, ISLR2-related
Mendeliome v1.3804 EMX2 Zornitza Stark edited their review of gene: EMX2: Changed rating: RED
Mendeliome v1.3804 EMX2 Zornitza Stark Classified gene: EMX2 as Red List (low evidence)
Mendeliome v1.3804 EMX2 Zornitza Stark Gene: emx2 has been classified as Red List (Low Evidence).
Mendeliome v1.3803 CRNKL1 Zornitza Stark Phenotypes for gene: CRNKL1 were changed from complex neurodevelopmental disorder MONDO:0100038 to Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, MIM# 621436
Mendeliome v1.3802 CRNKL1 Zornitza Stark reviewed gene: CRNKL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, MIM# 621436; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3802 TKFC Zornitza Stark edited their review of gene: TKFC: Changed publications: 32004446, 38697782
Mendeliome v1.3802 THG1L Zornitza Stark Classified gene: THG1L as Amber List (moderate evidence)
Mendeliome v1.3802 THG1L Zornitza Stark Gene: thg1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3801 THG1L Zornitza Stark Tag founder tag was added to gene: THG1L.
Mendeliome v1.3801 THG1L Zornitza Stark edited their review of gene: THG1L: Changed rating: AMBER
Mendeliome v1.3801 THG1L Zornitza Stark commented on gene: THG1L: LIMITED by ClinGen. Founder variant.
Mendeliome v1.3801 SUPV3L1 Zornitza Stark Marked gene: SUPV3L1 as ready
Mendeliome v1.3801 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3801 Zornitza Stark Copied gene SUPV3L1 from panel Mitochondrial disease
Mendeliome v1.3801 SUPV3L1 Zornitza Stark gene: SUPV3L1 was added
gene: SUPV3L1 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SUPV3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPV3L1 were set to 39596606; 35023579
Phenotypes for gene: SUPV3L1 were set to Mitochondrial disease, MONDO:0044970
Mendeliome v1.3800 SUCLG2 Zornitza Stark Marked gene: SUCLG2 as ready
Mendeliome v1.3800 SUCLG2 Zornitza Stark Gene: suclg2 has been classified as Red List (Low Evidence).
Mendeliome v1.3800 Zornitza Stark Copied gene SUCLG2 from panel Mitochondrial disease
Mendeliome v1.3800 SUCLG2 Zornitza Stark gene: SUCLG2 was added
gene: SUCLG2 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SUCLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SUCLG2 were set to 33484326
Phenotypes for gene: SUCLG2 were set to Mitochondrial disease, MONDO:0044970
Mendeliome v1.3799 SMDT1 Zornitza Stark Marked gene: SMDT1 as ready
Mendeliome v1.3799 SMDT1 Zornitza Stark Gene: smdt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3799 Zornitza Stark Copied gene SMDT1 from panel Mitochondrial disease
Mendeliome v1.3799 SMDT1 Zornitza Stark gene: SMDT1 was added
gene: SMDT1 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SMDT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMDT1 were set to 37454773
Phenotypes for gene: SMDT1 were set to Mitochondrial disease, MONDO:0044970, SMDT1-related
Mendeliome v1.3798 NDUFA3 Zornitza Stark Marked gene: NDUFA3 as ready
Mendeliome v1.3798 NDUFA3 Zornitza Stark Gene: ndufa3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3798 Zornitza Stark Copied gene NDUFA3 from panel Mitochondrial disease
Mendeliome v1.3798 NDUFA3 Zornitza Stark gene: NDUFA3 was added
gene: NDUFA3 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NDUFA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA3 were set to 41038977; 39661167
Phenotypes for gene: NDUFA3 were set to Mitochondrial disease, MONDO:0044970,NDUFA3-related
Mendeliome v1.3797 C19orf70 Zornitza Stark Tag new gene name tag was added to gene: C19orf70.
Mendeliome v1.3797 DNAJA3 Zornitza Stark Marked gene: DNAJA3 as ready
Mendeliome v1.3797 DNAJA3 Zornitza Stark Gene: dnaja3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3797 Zornitza Stark Copied gene DNAJA3 from panel Mitochondrial disease
Mendeliome v1.3797 DNAJA3 Zornitza Stark gene: DNAJA3 was added
gene: DNAJA3 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DNAJA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJA3 were set to 34750646; 30770860
Phenotypes for gene: DNAJA3 were set to Mitochondrial disease, MONDO:0044970, DNAJA3-related
Mendeliome v1.3796 NDUFA4 Zornitza Stark Tag new gene name tag was added to gene: NDUFA4.
Mendeliome v1.3796 NDUFA4 Zornitza Stark commented on gene: NDUFA4: New HGNC approved name is COXFA4
Mendeliome v1.3796 NHP2 Zornitza Stark Publications for gene: NHP2 were set to 18523010; 31985013
Mendeliome v1.3795 NHP2 Zornitza Stark edited their review of gene: NHP2: Added comment: LIMITED by ClinGen Interstitial Lung Disease panel but note two additional families reported in 2025, albeit with limited additional evidence for pathogenicity.; Changed publications: 18523010, 31985013, 40352450, 40073202
Mendeliome v1.3795 NEB Sangavi Sivagnanasundram edited their review of gene: NEB: Added comment: MOI expansion and upgrade.
The majority (≈140 families) present with recessive nebulin‑associated nemaline myopathy; >4 unrelated families have a dominant distal myopathy caused by large heterozygous deletions with western‑blot confirmation of a truncated protein.

AD - Amber --> green: ClinGen Congenital Myopathies GCEP has still classified the dominant association as moderate.
AR - still green: Classified as Definitive by ClinGen Congenital Myopathy GCEP: https://search.clinicalgenome.org/CCID:005608; Changed rating: GREEN; Changed publications: 39802796, 30679003, 33933294, 40661861, 40517164, 36714460, 27933661; Changed phenotypes: autosomal dominant nebulin-related myopathy MONDO:1010152, nemaline myopathy 2 MONDO:0009725; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3795 HSPB6 Sarah Milton edited their review of gene: HSPB6: Added comment: HSPB6 encodes heat shock protein family B [small] member 6 and forms homodimers and heterodimers with other members of it's family. In skeletal muscle HSBP6 is thought to function in promoting smooth muscle relaxation through depolymerising actin cytoskeleton.

PMID: 41294008 describes one individual with adult onset cataract and progressive weakness. His similarly affected mother was not genetically tested. Muscle biopsy demonstrated rimmed vacuoles and accumulation of HSPB6.
Variant was a c terminal extension variant (c.464delC|p.(Pro155Argfs*25) which was thought to result in aggregation of protein and was absent from gnomAD v4.

Other similar extension variants present in gnomAD v4 were transfected into cell models with those that had unstable mRNA transcripts not recapitulating findings however one other demonstrated accumulation of protein in certain settings.

Further literature is required.; Changed publications: 41294008; Changed phenotypes: Myopathy, MONDO:0005336, HSPB6-related
Mendeliome v1.3795 HSPB6 Sarah Milton changed review comment from: HSPB6 encodes heat shock protein family B [small] member 6 and forms homodimers and heterodimers with other members of it's family. One of it's roles is in protecting against cellular stress.

PMID 29157081 reports 11 unrelated individuals with a recurrent missense variant c.29C>T|p.( with dilated cardiomyopathy. Supportive mouse models showed transgenic mice with this variant had early death, and cardiac muscle showed decreased contractility and increased cardiomyocyte apoptosis.

This variant is present in gnomAD at a frequency not compatible with rare Mendelian disease with 818 heterozygotes, 2 homozygotes and higher allele frequency in certain subpopulations.
As such further literature is required to establish it's role in disease.
Sources: Literature; to: HSPB6 encodes heat shock protein family B [small] member 6 and forms homodimers and heterodimers with other members of it's family. One of it's roles is in protecting against cellular stress.

PMID 29157081 reports 11 unrelated individuals with a recurrent missense variant c.29C>T|p.(Ser10Phe) with dilated cardiomyopathy. Supportive mouse models showed transgenic mice with this variant had early death, and cardiac muscle showed decreased contractility and increased cardiomyocyte apoptosis.

This variant is present in gnomAD at a frequency not compatible with rare Mendelian disease with 818 heterozygotes, 2 homozygotes and higher allele frequency in certain subpopulations.
As such further literature is required to establish it's role in disease.
Sources: Literature
Mendeliome v1.3795 HSPB6 Sarah Milton gene: HSPB6 was added
gene: HSPB6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HSPB6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HSPB6 were set to 29157081
Phenotypes for gene: HSPB6 were set to Dilated cardiomyopathy, MONDO:0005021, HSPB6-related
Review for gene: HSPB6 was set to RED
Added comment: HSPB6 encodes heat shock protein family B [small] member 6 and forms homodimers and heterodimers with other members of it's family. One of it's roles is in protecting against cellular stress.

PMID 29157081 reports 11 unrelated individuals with a recurrent missense variant c.29C>T|p.( with dilated cardiomyopathy. Supportive mouse models showed transgenic mice with this variant had early death, and cardiac muscle showed decreased contractility and increased cardiomyocyte apoptosis.

This variant is present in gnomAD at a frequency not compatible with rare Mendelian disease with 818 heterozygotes, 2 homozygotes and higher allele frequency in certain subpopulations.
As such further literature is required to establish it's role in disease.
Sources: Literature
Mendeliome v1.3794 COPZ1 Zornitza Stark edited their review of gene: COPZ1: Changed phenotypes: Neutropenia, severe congenital, 12, autosomal recessive, MIM# 621439
Mendeliome v1.3794 COPZ1 Zornitza Stark Phenotypes for gene: COPZ1 were changed from Severe congenital neutropenia, autosomal recessive, MONDO:0028226, COPZ1-related to Neutropenia, severe congenital, 12, autosomal recessive MIM# 621439
Mendeliome v1.3793 MT-RNR2 Zornitza Stark Marked gene: MT-RNR2 as ready
Mendeliome v1.3793 MT-RNR2 Zornitza Stark Gene: mt-rnr2 has been classified as Red List (Low Evidence).
Mendeliome v1.3793 Zornitza Stark Copied gene MT-RNR2 from panel Mitochondrial disease
Mendeliome v1.3793 MT-RNR2 Zornitza Stark gene: MT-RNR2 was added
gene: MT-RNR2 was added to Mendeliome. Sources: Expert Review Red,Literature,Expert Review
Mode of inheritance for gene gene: MT-RNR2 was set to MITOCHONDRIAL
Publications for gene: MT-RNR2 were set to 29233888; 17761147; 24367055
Phenotypes for gene: MT-RNR2 were set to mitochondrial disease MONDO:0044970, MT-RNR2-related
Mendeliome v1.3792 IRX4 Lucy Spencer Phenotypes for gene: IRX4 were changed from Ventricular septal defect to Congenital heart disease MONDO:0005453, IRX4-related
Mendeliome v1.3791 IQSEC3 Lucy Spencer Phenotypes for gene: IQSEC3 were changed from Intellectual disability to Intellectual disability MONDO:0001071, IQSEC3-related
Mendeliome v1.3790 IQSEC2 Lucy Spencer Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530
Mendeliome v1.3789 IQGAP3 Lucy Spencer Phenotypes for gene: IQGAP3 were changed from Hereditary neuropathy to Hereditary peripheral neuropathy MONDO:0020127, IQGAP3-related
Mendeliome v1.3788 IQCE Lucy Spencer Phenotypes for gene: IQCE were changed from Postaxial polydactyly to Polydactyly, postaxial, type A7 MIM#617642
Mendeliome v1.3787 INSR Lucy Spencer Phenotypes for gene: INSR were changed from Hyperinsulinemic hypoglycemia, familial, 5, MIM# 609968; Leprechaunism, MIM# 246200; Rabson-Mendenhall syndrome, MIM# 262190 to Hyperinsulinemic hypoglycemia, familial, 5, MIM# 609968; Donohue syndrome MIM#246200; Rabson-Mendenhall syndrome, MIM# 262190
Mendeliome v1.3786 IMPDH2 Lucy Spencer Phenotypes for gene: IMPDH2 were changed from Neurodevelopmental disorder with dystonia to Neurodevelopmental disorder (MONDO:0700092), IMPDH2-related
Mendeliome v1.3785 IMPDH1 Lucy Spencer Phenotypes for gene: IMPDH1 were changed from Leber congenital amaurosis 11 (MIM# 613837); Retinitis pigmentosa 10 (MIM# 180105) to IMPDH1-related retinopathy MONDO:1040051; Leber congenital amaurosis 11 (MIM# 613837); Retinitis pigmentosa 10 (MIM# 180105)
Mendeliome v1.3784 IMPDH1 Lucy Spencer commented on gene: IMPDH1
Mendeliome v1.3784 IMMP2L Lucy Spencer Phenotypes for gene: IMMP2L were changed from Autism to Autism MONDO:0005260, IMMP2L-related
Mendeliome v1.3783 ILK Lucy Spencer Phenotypes for gene: ILK were changed from Dilated cardiomyopathy to Dilated cardiomyopathy MONDO:0005021, ILK-related
Mendeliome v1.3782 IL2RG Lucy Spencer commented on gene: IL2RG
Mendeliome v1.3782 IL1RAP Lucy Spencer Phenotypes for gene: IL1RAP were changed from Steroid-sensitive nephrotic syndrome to Nephrotic syndrome of childhood - steroid sensitive MONDO:0044781, IL1RAP-related
Mendeliome v1.3781 IL12RB2 Lucy Spencer Phenotypes for gene: IL12RB2 were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency disease MONDO:0021094, IL12RB1-related
Mendeliome v1.3780 IL10 Lucy Spencer Phenotypes for gene: IL10 were changed from Diseases of Immune Dysregulation; Early-onset inflammatory bowel disease to Immune system disorder MONDO:0005046, IL10-related; IL10-related early-onset inflammatory bowel disease MONDO:0016542
Mendeliome v1.3779 IL10 Lucy Spencer commented on gene: IL10
Mendeliome v1.3779 IKBKG Lucy Spencer Phenotypes for gene: IKBKG were changed from Ectodermal dysplasia and immunodeficiency 1, MIM# 300291; Immunodeficiency 33 , MIM#300636; Incontinentia pigmenti, MIM# 308300; Autoinflammatory disease, systemic, X-linked, MIM# 301081 to IKBKG-related immunodeficiency with or without ectodermal dysplasia MONDO:0100162; Ectodermal dysplasia and immunodeficiency 1, MIM# 300291; Immunodeficiency 33 , MIM#300636; Incontinentia pigmenti, MIM# 308300; Autoinflammatory disease, systemic, X-linked, MIM# 301081
Mendeliome v1.3778 IKBKG Lucy Spencer commented on gene: IKBKG
Mendeliome v1.3778 IGHMBP2 Lucy Spencer Phenotypes for gene: IGHMBP2 were changed from Neuronopathy, distal hereditary motor, type VI, MIM# 604320; Charcot-Marie-Tooth disease, axonal, type 2S, MIM# 616155 to Hereditary peripheral neuropathy MONDO:0020127, IGHMBP2-related; Neuronopathy, distal hereditary motor, type VI, MIM# 604320; Charcot-Marie-Tooth disease, axonal, type 2S, MIM# 616155
Mendeliome v1.3777 IGHMBP2 Lucy Spencer commented on gene: IGHMBP2
Mendeliome v1.3777 IFT74 Lucy Spencer Phenotypes for gene: IFT74 were changed from Bardet-Biedl syndrome 20, MIM# 617119; Joubert syndrome 40, MIM# 619582; Spermatogenic failure 58, MIM# 619585 to Ciliopathy MONDO:0005308, IFT74-related; Bardet-Biedl syndrome 20, MIM# 617119; Joubert syndrome 40, MIM# 619582; Spermatogenic failure 58, MIM# 619585
Mendeliome v1.3776 IFT74 Lucy Spencer commented on gene: IFT74
Mendeliome v1.3776 IFT172 Lucy Spencer Phenotypes for gene: IFT172 were changed from Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome 20, MIM# 619471 to Ciliopathy MONDO:0005308, IFT172-related; Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome 20, MIM# 619471
Mendeliome v1.3775 IFT172 Lucy Spencer commented on gene: IFT172
Mendeliome v1.3775 IFT140 Lucy Spencer Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781; {Polycystic kidney disease 9, susceptibility to} MIM#621164; Cranioectodermal dysplasia 5, MIM# 621180 to IFT140-related recessive ciliopathy MONDO:0100509; Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781; {Polycystic kidney disease 9, susceptibility to} MIM#621164; Cranioectodermal dysplasia 5, MIM# 621180
Mendeliome v1.3774 IFT140 Lucy Spencer commented on gene: IFT140
Mendeliome v1.3774 IFRD1 Lucy Spencer Phenotypes for gene: IFRD1 were changed from Hereditary spastic paraplegia; peripheral neuropathy; ataxia to Hereditary spastic paraplegia MONDO:0019064, IFRD1-related
Mendeliome v1.3773 PLXNA1 Lucy Spencer Publications for gene: PLXNA1 were set to 34054129
Mendeliome v1.3772 PLXNA1 Lucy Spencer changed review comment from: All 3 de novo missense variants in Dworschak et al. (2021) are present in gnomad v4 with 21, 2 and 4 heterozygotes. There is an additional de novo patient in Park 2017 PMID: 28464511, however their variant is also present in gnomad v4 with 5 heterozygotes. There is no new literature supporting the dominant association

The monoallelic assertion for this gene is now RED, still GREEN for biallelic; to: All 3 de novo missense variants in Dworschak et al. (2021) are present in gnomad v4 with 21, 2 and 4 heterozygotes. There is an additional de novo patient in Park 2017 PMID: 28464511, however their variant is also present in gnomad v4 with 5 heterozygotes. There is no recent literature supporting the dominant association

The monoallelic assertion for this gene is now RED, still GREEN for biallelic
Mendeliome v1.3772 PLXNA1 Lucy Spencer edited their review of gene: PLXNA1: Changed rating: RED; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.3772 PLXNA1 Lucy Spencer changed review comment from: All 3 de novo missense variants in Dworschak et al. (2021) are present in gnomad v4 with 21, 2 and 4 heterozygotes. There is an additional de novo patient in Park 2017 PMID: 28464511, however their variant is also present in gnomad v4 with 5 heterozygotes. There is no new literature supporting the dominant association

The monoallelic assertion for this gene is now RED, still GREEN for biallelic; to: All 3 de novo missense variants in Dworschak et al. (2021) are present in gnomad v4 with 21, 2 and 4 heterozygotes. There is an additional de novo patient in Park 2017 PMID: 28464511, however their variant is also present in gnomad v4 with 5 heterozygotes. There is no new literature supporting the dominant association

The monoallelic assertion for this gene is now RED, still GREEN for biallelic
Mendeliome v1.3772 PLXNA1 Lucy Spencer Mode of inheritance for gene: PLXNA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3771 PLXNA1 Lucy Spencer commented on gene: PLXNA1
Mendeliome v1.3771 ICE1 Lucy Spencer Phenotypes for gene: ICE1 were changed from Intellectual disability, cerebral atrophy to Intellectual disability (MONDO:0001071), ICE1-related
Mendeliome v1.3770 IBA57 Lucy Spencer commented on gene: IBA57
Mendeliome v1.3770 HUWE1 Lucy Spencer Phenotypes for gene: HUWE1 were changed from Mental retardation, X-linked syndromic, Turner type; Say-Meyer syndrome; Juberg-Marsidi syndrome to Intellectual developmental disorder, X-linked syndromic, Turner type MIM#309590
Mendeliome v1.3769 HTRA1 Lucy Spencer Phenotypes for gene: HTRA1 were changed from {Macular degeneration, age-related, 7}, 6101493; {Macular degeneration, age-related, neovascular type}, 610149; CARASIL syndrome, 600142; Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779 to Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy 2 MIM#616779; Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 2 MIM#600142
Mendeliome v1.3768 HSPB1 Lucy Spencer commented on gene: HSPB1
Mendeliome v1.3768 HOXB6 Lucy Spencer Phenotypes for gene: HOXB6 were changed from Hypospadias to Hypospadias MONDO:0005345, HOXB6-related
Mendeliome v1.3767 FAM20B Sangavi Sivagnanasundram reviewed gene: FAM20B: Rating: GREEN; Mode of pathogenicity: None; Publications: 41277483, 30847897; Phenotypes: Desbuquois dysplasia MONDO:0015426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3767 Chirag Patel Added reviews for gene SLC15A4 from panel Pituitary hormone deficiency
Mendeliome v1.3766 Chirag Patel Added reviews for gene HHIP from panel Pituitary hormone deficiency
Mendeliome v1.3765 PRMT9 Lucy Spencer Phenotypes for gene: PRMT9 were changed from Neurodevelopmental disorder, MONDO:0100500, PRMT9-related to Neurodevelopmental disorder, MONDO:0700092, PRMT9-related
Mendeliome v1.3764 PRMT9 Lucy Spencer Publications for gene: PRMT9 were set to PMID: 38561334
Mendeliome v1.3763 PRMT9 Lucy Spencer Classified gene: PRMT9 as Green List (high evidence)
Mendeliome v1.3763 PRMT9 Lucy Spencer Gene: prmt9 has been classified as Green List (High Evidence).
Mendeliome v1.3762 PRMT9 Lucy Spencer reviewed gene: PRMT9: Rating: GREEN; Mode of pathogenicity: None; Publications: 41260215; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PRMT9-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3762 KCNQ3 Lucy Spencer changed review comment from: From ClinGen:

Definitive for DOMINANT complex neurodevelopmental disorder MONDO:0100038, KCNQ3-related - 24 probands across 7 publications, mostly de novo variants. Mutations are clustered at p.Arg227 and p.Arg230, with a gain of function mechanism PMID: 24851285.

Moderate for DOMINANT self-limited familial neonatal epilepsy (Seizures, benign neonatal, 2 (MIM#121201)) - 15 missense in 18 probands across 16 publications. Variants clustered in the pore region (S5, S6, and intervening loop) and result in loss of function of channel activity PMID: 24851285. Note- there are several NMD predicted variants in this gene with over 10 hets in gnomad.

Limited for RECESSIVE genetic developmental and epileptic encephalopathy MONDO:0100062, KCNQ3-related - 1 individual and 1 family from 2 publications with homozygous frameshifts PMID: 29852413; 31440727. All have seizures, various brain MRI findings, developmental delay and intellectual disability. The family had 3 similarly affected siblings, all homozygous for an NMD frameshift. The unrelated patient had a mildly affected uncle with learning difficulties and transient neonatal seizures, he was not tested for the variant.

A third recessive patient not reported by ClinGen PMID: 29383681: 7yo girl with seizures, severe neurological impairment, and developmental delay. Compound heterozygous for two missense variants Val359Leu and Asp542Asn. Patch clamp studies showed that expression of either variant alone did not affect current density, but co-expression of both variants lead to a significant current reduction.; to: From ClinGen:

Definitive for DOMINANT complex neurodevelopmental disorder MONDO:0100038, KCNQ3-related - 24 probands across 7 publications, mostly de novo variants. Mutations are clustered at p.Arg227 and p.Arg230, with a gain of function mechanism PMID: 24851285.

Moderate for DOMINANT self-limited familial neonatal epilepsy (Seizures, benign neonatal, 2 (MIM#121201)) - 15 missense in 18 probands across 16 publications. Variants clustered in the pore region (S5, S6, and intervening loop) and result in loss of function of channel activity PMID: 24851285. Note- there are several NMD predicted variants in this gene with over 10 hets in gnomad.

Limited for RECESSIVE genetic developmental and epileptic encephalopathy MONDO:0100062, KCNQ3-related - 1 individual and 1 family from 2 publications with homozygous frameshifts PMID: 29852413; 31440727. All have seizures, various brain MRI findings, developmental delay and intellectual disability. The family had 3 similarly affected siblings, all homozygous for an NMD frameshift. The unrelated patient had a mildly affected uncle with learning difficulties and transient neonatal seizures, he was not tested for the variant.

A third recessive patient not reported by ClinGen PMID: 29383681: 7yo girl with seizures, severe neurological impairment, and developmental delay. Compound heterozygous for two missense variants Val359Leu and Asp542Asn. Patch clamp studies showed that expression of either variant alone did not affect current density, but co-expression of both variants lead to a significant current reduction.

borderline amber/green for recessive
Mendeliome v1.3762 KCNQ3 Lucy Spencer Mode of inheritance for gene: KCNQ3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3761 KCNQ3 Lucy Spencer Publications for gene: KCNQ3 were set to 33337327
Mendeliome v1.3760 KCNQ3 Lucy Spencer Phenotypes for gene: KCNQ3 were changed from Seizures, benign neonatal, 2, MIM# 121201 to Complex neurodevelopmental disorder MONDO:0100038, KCNQ3-related; Seizures, benign neonatal, 2 MIM#121201; genetic developmental and epileptic encephalopathy MONDO:0100062, KCNQ3-related
Mendeliome v1.3759 KCNQ3 Lucy Spencer reviewed gene: KCNQ3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24851285, 29852413, 31440727; Phenotypes: Complex neurodevelopmental disorder MONDO:0100038, KCNQ3-related, Seizures, benign neonatal, 2 MIM#121201, genetic developmental and epileptic encephalopathy MONDO:0100062, KCNQ3-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3759 SLC39A8 Zornitza Stark Phenotypes for gene: SLC39A8 were changed from Congenital disorder of glycosylation, type IIn , MIM#16721 to Congenital disorder of glycosylation, type IIn , MIM#616721
Mendeliome v1.3758 SLC39A8 Zornitza Stark edited their review of gene: SLC39A8: Changed phenotypes: Congenital disorder of glycosylation, type IIn , MIM#616721
Mendeliome v1.3758 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Charcot-Marie-Tooth disease, axonal, type 2II , MIM#620068 to Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#218000; Charcot-Marie-Tooth disease, axonal, type 2II , MIM#620068
Mendeliome v1.3757 RSPRY1 Zornitza Stark Phenotypes for gene: RSPRY1 were changed from Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585 to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, MIM# 616723
Mendeliome v1.3756 RSPRY1 Zornitza Stark edited their review of gene: RSPRY1: Changed phenotypes: Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, MIM# 616723
Mendeliome v1.3756 POPDC2 Zornitza Stark Phenotypes for gene: POPDC2 were changed from Sinoatrial node disorder, MONDO:0000469, POPDC2-related to Cardiac conduction disease with or without cardiomyopathy 2, MIM# 621367
Mendeliome v1.3755 POPDC2 Zornitza Stark Publications for gene: POPDC2 were set to
Mendeliome v1.3754 POPDC2 Zornitza Stark reviewed gene: POPDC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiac conduction disease with or without cardiomyopathy 2, MIM# 621367; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3754 ESRRG Zornitza Stark Marked gene: ESRRG as ready
Mendeliome v1.3754 ESRRG Zornitza Stark Gene: esrrg has been classified as Green List (High Evidence).
Mendeliome v1.3754 ESRRG Zornitza Stark Classified gene: ESRRG as Green List (high evidence)
Mendeliome v1.3754 ESRRG Zornitza Stark Gene: esrrg has been classified as Green List (High Evidence).
Mendeliome v1.3753 ESRRG Zornitza Stark gene: ESRRG was added
gene: ESRRG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ESRRG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ESRRG were set to 41265451
Phenotypes for gene: ESRRG were set to Movement disorder, MONDO:0005395, ESRRG-related
Review for gene: ESRRG was set to GREEN
Added comment: Eight individuals from seven unrelated families reported with heterozygous, mostly de novo variants in ESRRG: c.410G>A (p.Gly137Glu), c.446A>G (p.Lys149Arg), c.539G>A (p.Cys180Tyr), c.550C>T (p.Arg184Cys), c.1346T>G (p.Leu449Arg), and c.1352dup (p.Leu451Phefs∗38). All individuals had motor developmental delay, muscular hypotonia, and eye movement disorders, as well as congenital ataxia or gait imbalance. Other symptoms included joint hyperflexibility, dysarthria, myopia, and growth delay. Supportive functional data.
Sources: Literature
Mendeliome v1.3752 ELMSAN1 Zornitza Stark Marked gene: ELMSAN1 as ready
Mendeliome v1.3752 ELMSAN1 Zornitza Stark Gene: elmsan1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3752 ELMSAN1 Zornitza Stark Classified gene: ELMSAN1 as Amber List (moderate evidence)
Mendeliome v1.3752 ELMSAN1 Zornitza Stark Gene: elmsan1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3751 ELMSAN1 Zornitza Stark gene: ELMSAN1 was added
gene: ELMSAN1 was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: ELMSAN1.
Mode of inheritance for gene: ELMSAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ELMSAN1 were set to Neurodevelopmental disorder, MONDO:0700092, ELMSAN1-related
Review for gene: ELMSAN1 was set to AMBER
Added comment: PMID 41290615 reports 2 individuals from 2 unrelated families with the same heterozygous de novo missense variant p.Tyr654Ser presenting with a neurodevelopmental disorder characterized by speech delay, joint contractures, dysmorphic facial features, and gastrointestinal dysmotility. Functional studies demonstrated that the Y654S variant lies in an auto‑inhibitory loop of the MiDAC HDAC complex, causes a 3‑5‑fold increase in deacetylase activity, shows increased phosphorylation, and leads to reciprocal gene‑expression changes in patient fibroblasts versus loss‑of‑function models.

New HGNC approved name is MIDEAS.
Sources: Literature
Mendeliome v1.3750 SUCO Zornitza Stark Phenotypes for gene: SUCO were changed from Osteogenesis imperfecta, MONDO:0019019, SUCO-related to Syndromic disease (MONDO:0002254), SUCO-related
Mendeliome v1.3749 SUCO Zornitza Stark Publications for gene: SUCO were set to 29620724; 20440000
Mendeliome v1.3748 SUCO Zornitza Stark Classified gene: SUCO as Green List (high evidence)
Mendeliome v1.3748 SUCO Zornitza Stark Gene: suco has been classified as Green List (High Evidence).
Mendeliome v1.3747 SUCO Zornitza Stark edited their review of gene: SUCO: Added comment: PMID 41282771: 13 individuals from 6 families reported with bi-allelic variants in this gene and features of spastic CP and OI. Identified variants included 2 truncating, 3 missense, and 3 canonical splice site variants. SUCO knockout (KO) (Opt −/−) mice display impaired bone formation and spontaneous fractures but also have evidence of a neurological phenotype with imbalanced gait and an impaired righting response. Drosophila model system using nervous system-specific RNAi knockdown of the SUCO ortholog (CG31678) showed neurological impairments occur independent of skeletal phenotypes.; Changed rating: GREEN; Changed publications: 20440000, 41282771; Changed phenotypes: Syndromic disease (MONDO:0002254), SUCO-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3747 KCTD1 Zornitza Stark Phenotypes for gene: KCTD1 were changed from Scalp-ear-nipple syndrome MIM#181270 to Scalp-ear-nipple syndrome MIM#181270; Dental radicular dysplasia, MIM# 621434
Mendeliome v1.3746 KCTD1 Zornitza Stark Publications for gene: KCTD1 were set to 23541344; 31324836
Mendeliome v1.3745 KCTD1 Zornitza Stark reviewed gene: KCTD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38791218; Phenotypes: Dental radicular dysplasia, MIM# 621434; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3745 GTF2H4 Zornitza Stark Marked gene: GTF2H4 as ready
Mendeliome v1.3745 GTF2H4 Zornitza Stark Gene: gtf2h4 has been classified as Red List (Low Evidence).
Mendeliome v1.3745 Zornitza Stark Copied gene GTF2H4 from panel Photosensitivity Syndromes
Mendeliome v1.3745 GTF2H4 Zornitza Stark gene: GTF2H4 was added
gene: GTF2H4 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: GTF2H4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF2H4 were set to 40924495; 40924475
Phenotypes for gene: GTF2H4 were set to Xeroderma pigmentosum, complementation group J, MIM# 621435
Mendeliome v1.3744 OPA1 Zornitza Stark Phenotypes for gene: OPA1 were changed from Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type)MIM# 616896; Behr syndrome MIM#210000, AR; Optic atrophy 1, MIM#165500; Optic atrophy plus syndrome, MIM# 125250 to OPA1-related optic atrophy with or without extraocular features, MONDO:0800181
Mendeliome v1.3743 OPA1 Zornitza Stark Publications for gene: OPA1 were set to 30165240
Mendeliome v1.3743 OPA1 Zornitza Stark Publications for gene: OPA1 were set to
Mendeliome v1.3743 Zornitza Stark Added reviews for gene OPA1 from panel Mitochondrial disease
Mendeliome v1.3742 Zornitza Stark Added reviews for gene PPM1K from panel Aminoacidopathy
Mendeliome v1.3741 HSPA9 Zornitza Stark edited their review of gene: HSPA9: Added comment: PMID 39196378: another three individuals reported albeit with little supportive data.; Changed rating: GREEN; Changed publications: 26491070, 39196378
Mendeliome v1.3741 FGD5 Zornitza Stark Marked gene: FGD5 as ready
Mendeliome v1.3741 FGD5 Zornitza Stark Gene: fgd5 has been classified as Red List (Low Evidence).
Mendeliome v1.3741 Chirag Patel Added reviews for gene ARNT2 from panel Mendeliome
Mendeliome v1.3740 ESRP2 Chirag Patel Classified gene: ESRP2 as Amber List (moderate evidence)
Mendeliome v1.3740 ESRP2 Chirag Patel Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3740 ESRP2 Chirag Patel Classified gene: ESRP2 as Amber List (moderate evidence)
Mendeliome v1.3740 ESRP2 Chirag Patel Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3739 MT-ND2 Zornitza Stark Tag mtDNA tag was added to gene: MT-ND2.
Mendeliome v1.3739 MT-CO3 Zornitza Stark Marked gene: MT-CO3 as ready
Mendeliome v1.3739 MT-CO3 Zornitza Stark Gene: mt-co3 has been classified as Green List (High Evidence).
Mendeliome v1.3739 MT-CO3 Zornitza Stark Publications for gene: MT-CO3 were set to 11063732; 33863631; 34054915; 8630495; 9634511; 12414820; 21163656; 16288875; 8630495; 9634511
Mendeliome v1.3738 MT-CO3 Zornitza Stark Tag mtDNA tag was added to gene: MT-CO3.
Mendeliome v1.3738 Zornitza Stark Copied gene MT-CO3 from panel Mitochondrial disease
Mendeliome v1.3738 MT-CO3 Zornitza Stark gene: MT-CO3 was added
gene: MT-CO3 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene gene: MT-CO3 was set to MITOCHONDRIAL
Publications for gene: MT-CO3 were set to 11063732; 33863631; 34054915; 8630495; 9634511; 12414820; 21163656; 16288875; 8630495; 9634511
Phenotypes for gene: MT-CO3 were set to Mitochondrial disease MONDO:0044970, MT-CO3-related
Mendeliome v1.3737 HMGCS1 Zornitza Stark Phenotypes for gene: HMGCS1 were changed from Rigid spine syndrome, MONDO:0019951, HMGCS1-related to Congenital myopathy 28 with rigid spine, MIM# 621433
Mendeliome v1.3736 HMGCS1 Zornitza Stark edited their review of gene: HMGCS1: Changed phenotypes: Congenital myopathy 28 with rigid spine, MIM# 621433
Mendeliome v1.3736 MT-ATP8 Zornitza Stark Classified gene: MT-ATP8 as Amber List (moderate evidence)
Mendeliome v1.3736 MT-ATP8 Zornitza Stark Gene: mt-atp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3735 MT-ATP8 Zornitza Stark edited their review of gene: MT-ATP8: Changed publications: 40112238, 24153443, 20207608, 32858252, 33340416, 32858252, 19759059, 22919063
Mendeliome v1.3735 MT-ATP8 Zornitza Stark edited their review of gene: MT-ATP8: Changed rating: AMBER
Mendeliome v1.3735 MT-ATP8 Zornitza Stark Deleted their comment
Mendeliome v1.3735 MT-ATP8 Zornitza Stark commented on gene: MT-ATP8: LIMITED by ClinGen. Three variants (m.8403T>C, m.8411A>G, m.8424T>C) have been reported in three individuals. Age of onset varied from birth to the 30s. Clinical features included muscle weakness, wasting, and cramping; dysarthria, headache, periodic paralysis, seizures, mood disorder, neuropathy, pancreatitis, diarrhoea, and weight loss. Brain imaging revealed cerebellar atrophy; lactate was elevated. The gene-disease relationship is also supported by a biochemical function (complex V subunit) shared with other genes associated with primary mitochondrial disease, functional alteration in non-patient cells, and model organisms.
Mendeliome v1.3735 FASTKD5 Zornitza Stark Phenotypes for gene: FASTKD5 were changed from Leigh syndrome MONDO:0009723, FASTKD5-related to Mitochondrial complex IV deficiency, nuclear type 24, MIM# 621431
Mendeliome v1.3734 FASTKD5 Zornitza Stark reviewed gene: FASTKD5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 24, MIM# 621431; Mode of inheritance: None
Mendeliome v1.3734 COL10A1 Zornitza Stark Publications for gene: COL10A1 were set to 15880705; 31633898
Mendeliome v1.3733 COL10A1 Zornitza Stark edited their review of gene: COL10A1: Changed publications: 15880705, 31633898, 31348255, 25542771
Mendeliome v1.3733 COL10A1 Zornitza Stark changed review comment from: Note: Gene reviews also notes severe lethal phenotypes in recessive inheritance where parents were only mildly affected, however only 2 unrelated families reported to date (PMID: 31633898). Both haploinsufficiency and dominant-negative mechanisms have been suggested to cause disease (OMIM, PMID: 15880705, PMID: 31633898). “Pathogenic variants in COL10A1 are clustered in the C-terminal non-collagenous (NC1) domain, which contains motifs required for normal assembly of the collagen trimer. Both missense and truncating (frameshift and nonsense) variants in COL10A1 cause collagen X protein misfolding during protein synthesis, resulting in a failure of trimerization and aggregation within the endoplasmic reticulum (ER) of hypertrophic chondrocytes. Resultant ER stress, activation of the unfolded protein response, and reduced levels of functional type X collagen in the growth plate cause chondrodysplasia and development of the SMCD phenotype [Rajpar et al 2009].” -> from Gene Reviews (PMID: 31633898). Some pathogenic missense also reported in the N-terminal signal peptide (Decipher), however please note that to date, no Gly-X-Y substitutions in the collagen triple helix repeats have yet been reported, pathogenic or otherwise.; to: Note: Gene reviews also notes severe lethal phenotypes in recessive inheritance where parents were only mildly affected, however only 2 unrelated families reported to date (PMID: 31633898). Both haploinsufficiency and dominant-negative mechanisms have been suggested to cause disease (OMIM, PMID: 15880705, PMID: 31633898). “Pathogenic variants in COL10A1 are clustered in the C-terminal non-collagenous (NC1) domain, which contains motifs required for normal assembly of the collagen trimer. Both missense and truncating (frameshift and nonsense) variants in COL10A1 cause collagen X protein misfolding during protein synthesis, resulting in a failure of trimerization and aggregation within the endoplasmic reticulum (ER) of hypertrophic chondrocytes. Resultant ER stress, activation of the unfolded protein response, and reduced levels of functional type X collagen in the growth plate cause chondrodysplasia and development of the SMCD phenotype [Rajpar et al 2009].” -> from Gene Reviews (PMID: 31633898). Some pathogenic missense also reported in the N-terminal signal peptide (Decipher).

Note that unlike with other collagens, Gly-X-Y substitutions in the collagen triple helix repeats are very rarely reported as disease-causing, and may result in a milder phenotype (PMID 31348255; 25542771). These should be interpreted with caution.
Mendeliome v1.3733 TBXAS1 Zornitza Stark Publications for gene: TBXAS1 were set to
Mendeliome v1.3732 TBXAS1 Zornitza Stark edited their review of gene: TBXAS1: Added comment: PMID 27156553, 28868793, 33244729, 33595912, 36786374, 39220787 and 39277773 together report 10 individuals from 8 unrelated families with biallelic loss‑of‑function variants in TBXAS1. Clinical features include anemia/pancytopenia, thrombocytopenia, bone‑marrow fibrosis, splenomegaly and markedly increased diaphyseal bone density, often responding to steroids.; Changed publications: 18264100, 27156553, 28868793, 33244729, 33595912, 36786374, 39220787, 39277773
Mendeliome v1.3732 ADAMTSL2 Zornitza Stark Phenotypes for gene: ADAMTSL2 were changed from Geleophysic dysplasia 1, MIM# 231050; Dermatosparaxic Ehlers Danlos syndrome to Geleophysic dysplasia 1, MIM# 231050; Dermatosparaxic Ehlers Danlos syndrome; Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356)
Mendeliome v1.3731 ADAMTSL2 Zornitza Stark edited their review of gene: ADAMTSL2: Added comment: PMID 36896612: 12 individuals reported with the severe end of the spectrum of ADAMTSL2-related skeletal dysplasia. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly.; Changed publications: 33369194, 26879370, 21415077, 36896612; Changed phenotypes: Geleophysic dysplasia 1, MIM# 231050, Dermatosparaxic Ehlers Danlos syndrome, Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356)
Mendeliome v1.3731 MED16 Lucy Spencer Phenotypes for gene: MED16 were changed from complex neurodevelopmental disorder MONDO:0100038 to Guillouet-Gordon syndrome MIM#621220
Mendeliome v1.3730 MED16 Lucy Spencer reviewed gene: MED16: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Guillouet-Gordon syndrome MIM#621220; Mode of inheritance: None
Mendeliome v1.3730 CSNK1G1 Zornitza Stark edited their review of gene: CSNK1G1: Changed rating: AMBER
Mendeliome v1.3730 CSNK1G1 Zornitza Stark commented on gene: CSNK1G1: Gene-disease relationship reviewed again. No new literature in last 5 years. Only one LP assertion in ClinVar by 3billion. LoF variants in population. Downgrade to Amber.
Mendeliome v1.3730 CSNK1G1 Zornitza Stark Classified gene: CSNK1G1 as Amber List (moderate evidence)
Mendeliome v1.3730 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3729 Bryony Thompson Added reviews for gene COQ7 from panel Hereditary Spastic Paraplegia
Mendeliome v1.3728 ABI2 Zornitza Stark Marked gene: ABI2 as ready
Mendeliome v1.3728 ABI2 Zornitza Stark Gene: abi2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3728 Zornitza Stark Copied gene ABI2 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3728 ABI2 Zornitza Stark gene: ABI2 was added
gene: ABI2 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ABI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABI2 were set to 40475134
Phenotypes for gene: ABI2 were set to Neurodevelopmental disorder, MONDO:0700092, ABI2-related
Mendeliome v1.3727 Bryony Thompson Added reviews for gene PLD3 from panel Ataxia
Mendeliome v1.3726 HOXA4 Lucy Spencer Phenotypes for gene: HOXA4 were changed from Microtia-Atresia; CAKUT to Microtia with meatal atresia and conductive deafness MONDO:0009634, HOXA4-related
Mendeliome v1.3725 HNRNPD Lucy Spencer Phenotypes for gene: HNRNPD were changed from Neurodevelopmental disorder to Complex neurodevelopmental disorder MONDO:0100038, HNRNPD-related
Mendeliome v1.3724 HMBS Lucy Spencer commented on gene: HMBS
Mendeliome v1.3724 HIRA Lucy Spencer Phenotypes for gene: HIRA were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, HIRA-related
Mendeliome v1.3723 HID1 Lucy Spencer Phenotypes for gene: HID1 were changed from Syndromic infantile encephalopathy; Hypopituitarism to Developmental and epileptic encephalopathy 105 with hypopituitarism MIM#619983
Mendeliome v1.3722 HIBADH Lucy Spencer Phenotypes for gene: HIBADH were changed from Organic aciduria to 3-hydroxyisobutyric aciduria MONDO:0009371, HIBADH-related
Mendeliome v1.3721 HIBADH Lucy Spencer Classified gene: HIBADH as Green List (high evidence)
Mendeliome v1.3721 HIBADH Lucy Spencer Gene: hibadh has been classified as Green List (High Evidence).
Mendeliome v1.3720 HIBADH Lucy Spencer reviewed gene: HIBADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 35174513, 34176136; Phenotypes: 3-hydroxyisobutyric aciduria MONDO:0009371, HIBADH-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3720 HELQ Lucy Spencer Phenotypes for gene: HELQ were changed from Primary ovarian insufficiency to Primary ovarian insufficiency MONDO:0005387, HELQ-related
Mendeliome v1.3719 HEATR5B Lucy Spencer Phenotypes for gene: HEATR5B were changed from pontocerebellar hypoplasia; intellectual disability; seizures to Pontocerebellar hypoplasia MONDO:0020135, HEATR5B-related
Mendeliome v1.3718 HDAC4 Lucy Spencer Phenotypes for gene: HDAC4 were changed from Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability; Intellectual disability syndrome to Neurodevelopmental disorder with central hypotonia and dysmorphic facies MIM#619797; Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability; Intellectual disability syndrome
Mendeliome v1.3717 HCN1 Lucy Spencer commented on gene: HCN1
Mendeliome v1.3717 H3F3B Lucy Spencer Phenotypes for gene: H3F3B were changed from Intellectual disability; regression; seizures to Bryant-Li-Bhoj neurodevelopmental syndrome 2 MIM#619721
Mendeliome v1.3716 H3F3A Lucy Spencer Phenotypes for gene: H3F3A were changed from Intellectual disability; regression; seizures to Bryant-Li-Bhoj neurodevelopmental syndrome 1 MIM#619720
Mendeliome v1.3715 GUCY2D Lucy Spencer Phenotypes for gene: GUCY2D were changed from Cone-rod dystrophy 6, MIM# 601777; Leber congenital amaurosis 1, MIM# 204000; Night blindness, congenital stationary, type 1I, MIM# 618555 to GUCY2D-related dominant retinopathy MONDO:0100441; GUCY2D-related recessive retinopathy MONDO:0100453
Mendeliome v1.3714 GUCY2D Lucy Spencer reviewed gene: GUCY2D: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: GUCY2D-related dominant retinopathy MONDO:0100441, GUCY2D-related recessive retinopathy MONDO:0100453; Mode of inheritance: None
Mendeliome v1.3714 GSS Lucy Spencer Phenotypes for gene: GSS were changed from Glutathione synthetase deficiency MIM#266130; Hemolytic anemia due to glutathione synthetase deficiency MIM#231900; Disorders of the gamma-glutamyl cycle to inherited glutathione synthetase deficiency MONDO:0017909; Glutathione synthetase deficiency MIM#266130; Hemolytic anemia due to glutathione synthetase deficiency MIM#231900
Mendeliome v1.3713 GSPT2 Lucy Spencer Phenotypes for gene: GSPT2 were changed from Intellectual disability to Intellectual disability MONDO:0001071, GSPT2-related
Mendeliome v1.3712 GRIN2B Lucy Spencer Phenotypes for gene: GRIN2B were changed from Mental retardation, autosomal dominant 6, MIM# 613970; Epileptic encephalopathy, early infantile, 27, MIM# 616139 to GRIN2B-related complex neurodevelopmental disorder MONDO:0700350; Developmental and epileptic encephalopathy 27 MIM#616139; Intellectual developmental disorder, autosomal dominant 6, with or without seizures MIM#613970
Mendeliome v1.3711 GRIN2B Lucy Spencer reviewed gene: GRIN2B: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: GRIN2B-related complex neurodevelopmental disorder MONDO:0700350; Mode of inheritance: None
Mendeliome v1.3711 GRIN1 Lucy Spencer Phenotypes for gene: GRIN1 were changed from Developmental and epileptic encephalopathy 101, MIM# 619814; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820 to GRIN1-related complex neurodevelopmental disorder MONDO:1060123; Developmental and epileptic encephalopathy 101, MIM# 619814; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820
Mendeliome v1.3710 GRIN1 Lucy Spencer reviewed gene: GRIN1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: GRIN1-related complex neurodevelopmental disorder MONDO:1060123; Mode of inheritance: None
Mendeliome v1.3710 GRIK2 Lucy Spencer Phenotypes for gene: GRIK2 were changed from Mental retardation, autosomal recessive, 6 MIM# 611092; Neurodevelopmental disorder with impaired language and ataxia and with or without seizures, MIM# 619580 to Intellectual developmental disorder, autosomal recessive 6 MIM#611092; Neurodevelopmental disorder with impaired language and ataxia and with or without seizures MIM#619580
Mendeliome v1.3709 GPR161 Lucy Spencer Phenotypes for gene: GPR161 were changed from Predisposition to paediatric medulloblastoma to Medulloblastoma predisposition syndrome MIM#155255
Mendeliome v1.3708 GPR143 Lucy Spencer Phenotypes for gene: GPR143 were changed from GPR143-related foveal hypoplasia MONDO:0700230; congenital nystagmus 6, MIM 300814; type I ocular albinism, Nettleship-Falls type, MIM 300500 to GPR143-related foveal hypoplasia MONDO:0700230; congenital nystagmus 6, MIM# 300814; Ocular albinism, type I, Nettleship-Falls type, MIM# 300500
Mendeliome v1.3707 GPR143 Lucy Spencer Phenotypes for gene: GPR143 were changed from congenital nystagmus 6, MIM 300814; type I ocular albinism, Nettleship-Falls type, MIM 300500 to GPR143-related foveal hypoplasia MONDO:0700230; congenital nystagmus 6, MIM 300814; type I ocular albinism, Nettleship-Falls type, MIM 300500
Mendeliome v1.3706 GPR143 Lucy Spencer reviewed gene: GPR143: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: GPR143-related foveal hypoplasia MONDO:0700230; Mode of inheritance: None
Mendeliome v1.3706 GOLGA3 Lucy Spencer Phenotypes for gene: GOLGA3 were changed from Primary ciliary dyskinesia to Primary ciliary dyskinesia MONDO:0016575, GOLGA3-related
Mendeliome v1.3705 GNPTAB Lucy Spencer Phenotypes for gene: GNPTAB were changed from GNPTAB-mucolipidosis MONDO:0100122; Mucolipidosis II alpha/beta, MIM# 252500; MONDO:0009650; Mucolipidosis III alpha/beta, MIM# 252600; MONDO:0018931 to GNPTAB-mucolipidosis MONDO:0100122; Mucolipidosis II alpha/beta, MIM# 252500; Mucolipidosis III alpha/beta, MIM# 252600
Mendeliome v1.3704 GNPTAB Lucy Spencer Phenotypes for gene: GNPTAB were changed from Mucolipidosis II alpha/beta, MIM# 252500; MONDO:0009650; Mucolipidosis III alpha/beta, MIM# 252600; MONDO:0018931 to GNPTAB-mucolipidosis MONDO:0100122; Mucolipidosis II alpha/beta, MIM# 252500; MONDO:0009650; Mucolipidosis III alpha/beta, MIM# 252600; MONDO:0018931
Mendeliome v1.3703 GNPTAB Lucy Spencer reviewed gene: GNPTAB: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: GNPTAB-mucolipidosis MONDO:0100122; Mode of inheritance: None
Mendeliome v1.3703 GNB5 Lucy Spencer Phenotypes for gene: GNB5 were changed from Intellectual developmental disorder with cardiac arrhythmia, 617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182; Early infantile epileptic encephalopathy (EIEE) to gnb5-related intellectual disability-cardiac arrhythmia syndrome MONDO:0014953; Lodder-Merla syndrome, type 1, with impaired intellectual development and cardiac arrhythmia (MIM#617173); Lodder-Merla syndrome, type 2, with developmental delay and with or without cardiac arrhythmia (MIM#617182)
Mendeliome v1.3702 GNB5 Lucy Spencer reviewed gene: GNB5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: gnb5-related intellectual disability-cardiac arrhythmia syndrome MONDO:0014953; Mode of inheritance: None
Mendeliome v1.3702 GMPPB Lucy Spencer Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352) to Myopathy caused by variation in GMPPB MONDO:0700084; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Mendeliome v1.3701 FDFT1 Bryony Thompson Phenotypes for gene: FDFT1 were changed from squalene synthase deficiency MONDO:0032566 to squalene synthase deficiency MONDO:0032566; porokeratosis MONDO:0006602, FDFT1-related
Mendeliome v1.3700 FDFT1 Bryony Thompson Publications for gene: FDFT1 were set to 29909962
Mendeliome v1.3699 FDFT1 Bryony Thompson Mode of inheritance for gene: FDFT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3698 FDFT1 Bryony Thompson edited their review of gene: FDFT1: Added comment: PMID: 38653249 - Skin lesions of 2 individuals with generalised porokeratosis had germline and lesion-specific somatic variants on opposite alleles in FDFT1, representing FDFT1-associated hereditary porokeratosis. Whereas, lesions of the solitary or linearly arranged localised form in 6 individuals had somatic biallelic promoter hypermethylation or monoallelic promoter hypermethylation with somatic genetic alterations on opposite alleles in FDFT1, indicating non-hereditary porokeratosis - gene-specific somatic epigenetic mosaicism. Porokeratosis is characterised as an autoinflammatory keratinisation disease; Changed publications: 29909962, 38653249; Changed phenotypes: squalene synthase deficiency MONDO:0032566, porokeratosis MONDO:0006602, FDFT1-related; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3698 FDPS Bryony Thompson Marked gene: FDPS as ready
Mendeliome v1.3698 FDPS Bryony Thompson Gene: fdps has been classified as Green List (High Evidence).
Mendeliome v1.3698 FDPS Bryony Thompson Classified gene: FDPS as Green List (high evidence)
Mendeliome v1.3698 FDPS Bryony Thompson Gene: fdps has been classified as Green List (High Evidence).
Mendeliome v1.3697 FDPS Bryony Thompson gene: FDPS was added
gene: FDPS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FDPS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FDPS were set to 26202976; 30561051; 38283795; 41240373
Phenotypes for gene: FDPS were set to porokeratosis 9, multiple types MONDO:0014713
Review for gene: FDPS was set to GREEN
Added comment: PMID 26202976 reports 4 individuals from 4 families with autosomal dominant loss‑of‑function FDPS variants causing extensive porokeratosis; PMID 30561051 adds 2 affected individuals from 1 family with disseminated superficial actinic porokeratosis; PMID 38283795 describes a single case of disseminated superficial porokeratosis; and PMID 41240373 reviews 22 individuals from the literature and an additional 3 families, with disseminated superficial actinic porokeratosis / disseminated superficial porokeratosis and genital porokeratosis.
Sources: Literature
Mendeliome v1.3696 HELB Zornitza Stark Marked gene: HELB as ready
Mendeliome v1.3696 HELB Zornitza Stark Gene: helb has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3696 HELB Rylee Peters Classified gene: HELB as Amber List (moderate evidence)
Mendeliome v1.3696 HELB Rylee Peters Gene: helb has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3695 HELB Rylee Peters gene: HELB was added
gene: HELB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HELB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HELB were set to 41212051
Phenotypes for gene: HELB were set to Premature ovarian failure, MONDO:0019852, HELB-related
Review for gene: HELB was set to AMBER
Added comment: PMID: 41212051 reports three individuals from a single family with a heterozygous missense HELB c.349G>T (p.Asp117Tyr) presenting with premature ovarian insufficiency and early menopause. The variant co-segregates with disease across three generations and is absent from population databases. A mouse knock-in model recapitulates the POI phenotype; RNA-seq and transcriptomic analysis showed dysregulation of genes associated with ovarian function in Helb-mutated mice.
Sources: Literature
Mendeliome v1.3694 NOS1 Chirag Patel Marked gene: NOS1 as ready
Mendeliome v1.3694 NOS1 Chirag Patel Gene: nos1 has been classified as Green List (High Evidence).
Mendeliome v1.3694 NOS1 Chirag Patel Classified gene: NOS1 as Green List (high evidence)
Mendeliome v1.3694 NOS1 Chirag Patel Gene: nos1 has been classified as Green List (High Evidence).
Mendeliome v1.3693 Chirag Patel Copied gene NOS1 from panel Pituitary hormone deficiency
Mendeliome v1.3693 NOS1 Chirag Patel gene: NOS1 was added
gene: NOS1 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOS1 were set to 36197968
Phenotypes for gene: NOS1 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.3692 COX4I1 Lucy Spencer Classified gene: COX4I1 as Green List (high evidence)
Mendeliome v1.3692 COX4I1 Lucy Spencer Gene: cox4i1 has been classified as Green List (High Evidence).
Mendeliome v1.3691 SLC6A9 Zornitza Stark Phenotypes for gene: SLC6A9 were changed from Glycine encephalopathy with normal serum glycine, MIM# 617301 to Glycine encephalopathy with normal serum glycine, MIM# 617301; Scoliosis, isolated, susceptibility to, 6, MIM# 621428
Mendeliome v1.3690 SLC6A9 Zornitza Stark Mode of inheritance for gene: SLC6A9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3689 SLC6A9 Zornitza Stark edited their review of gene: SLC6A9: Added comment: 26 patients from 5 families with adolescent idiopathic scoliosis. Plasma glycine concentration measured in 15 patients was elevated compared to that in 36 unaffected controls. In addition, surface electromyography in 2 affected children showed aberrant paraspinal muscle activity, which was not observed in affected adults, suggesting an etiology for the spinal curvature occurring during the developmental period.

Two different missense variants reported. Functional studies indicated a dominant negative effect. In zebrafish, mutant glyt1 protein was shown to exhibit dominant-negative effects over the wildtype protein. All slc6A9 hmz m/m fish died by 18 days postfertilization (dpf), whereas about half of the slc6A9 het m/+ fish survived to 30 dpf. Glycine levels were elevated in the slc6A9 m/m fish, and at 7 dpf the majority of the mutant fish had a lateral axial curvature. In addition, some of the slc6A9 m/+ fish also had a lateral axial curvature, which persisted through day 100 dpf. The spinal curvature was rescued by expression of wildtype SLC6A9 but not with expression of SLC6A9 with a Y206F or R662W mutation. Treatment of the slc6A9 m/m fish with benzoate, a glycine neutralizer, moderately improved the curvature phenotype; Changed publications: 27481395, 27773429, 14622582, 33269555, 37962965; Changed phenotypes: Glycine encephalopathy with normal serum glycine, MIM# 617301, Scoliosis, isolated, susceptibility to, 6, MIM# 621428; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3689 Chirag Patel Added reviews for gene GJA5 from panel Congenital Heart Defect
Mendeliome v1.3688 Chirag Patel Copied gene HDAC1 from panel Congenital Heart Defect
Mendeliome v1.3688 HDAC1 Chirag Patel gene: HDAC1 was added
gene: HDAC1 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: HDAC1.
Mode of inheritance for gene: HDAC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HDAC1 were set to Congenital heart disease, MONDO:0005453
Mendeliome v1.3687 TRA2B Zornitza Stark Phenotypes for gene: TRA2B were changed from Neurodevelopmental disorder, TRA2B-related, MONDO# 0700092 to Ramond-Elliott neurodevelopmental syndrome, MIM# 621421
Mendeliome v1.3686 TRA2B Zornitza Stark reviewed gene: TRA2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ramond-Elliott neurodevelopmental syndrome, MIM# 621421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3686 Chirag Patel Added reviews for gene DAND5 from panel Heterotaxy
Mendeliome v1.3685 Chirag Patel Added reviews for gene UGDH from panel Congenital Heart Defect
Mendeliome v1.3684 Chirag Patel Added reviews for gene NFATC2 from panel Congenital Heart Defect
Mendeliome v1.3684 Chirag Patel Copied gene PROX1 from panel Congenital Heart Defect
Mendeliome v1.3684 PROX1 Chirag Patel gene: PROX1 was added
gene: PROX1 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: PROX1.
Mode of inheritance for gene: PROX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PROX1 were set to Congenital heart disease, MONDO:0005453
Mendeliome v1.3683 Chirag Patel Copied gene RAI2 from panel Congenital Heart Defect
Mendeliome v1.3683 RAI2 Chirag Patel gene: RAI2 was added
gene: RAI2 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: RAI2.
Mode of inheritance for gene: RAI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAI2 were set to Congenital heart disease, MONDO:0005453
Mendeliome v1.3682 Chirag Patel Added reviews for gene NFATC1 from panel Congenital Heart Defect
Mendeliome v1.3681 Chirag Patel Added reviews for gene CTNNA3 from panel Congenital Heart Defect
Mendeliome v1.3680 Chirag Patel Copied gene NTRK3 from panel Congenital Heart Defect
Mendeliome v1.3680 NTRK3 Chirag Patel gene: NTRK3 was added
gene: NTRK3 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: NTRK3.
Mode of inheritance for gene: NTRK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NTRK3 were set to Congenital heart disease, MONDO:0005453
Mendeliome v1.3680 Chirag Patel Copied gene HEY1 from panel Congenital Heart Defect
Mendeliome v1.3680 HEY1 Chirag Patel gene: HEY1 was added
gene: HEY1 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: HEY1.
Mode of inheritance for gene: HEY1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HEY1 were set to Congenital heart disease, MONDO:0005453
Mendeliome v1.3679 OSR1 Chirag Patel changed review comment from: ClinGen DISPUTED - Aug 2024; to: ClinGen DISPUTED - Apr 2024
Mendeliome v1.3679 OSR1 Chirag Patel reviewed gene: OSR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3679 OSR1 Chirag Patel Mode of inheritance for gene: OSR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3679 OSR1 Chirag Patel Phenotypes for gene: OSR1 were changed from to Congenital heart disease, MONDO:0005453
Mendeliome v1.3678 Chirag Patel Added reviews for gene LEFTY2 from panel Congenital Heart Defect
Mendeliome v1.3677 Chirag Patel Copied gene CSRP1 from panel Congenital Heart Defect
Mendeliome v1.3677 CSRP1 Chirag Patel gene: CSRP1 was added
gene: CSRP1 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: CSRP1.
Mode of inheritance for gene: CSRP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CSRP1 were set to Congenital heart disease, MONDO:0005453
Mendeliome v1.3677 Chirag Patel Copied gene ATE1 from panel Congenital Heart Defect
Mendeliome v1.3677 ATE1 Chirag Patel gene: ATE1 was added
gene: ATE1 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: ATE1.
Mode of inheritance for gene: ATE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATE1 were set to Congenital heart disease, MONDO:0005453
Mendeliome v1.3676 FOXL1 Chirag Patel Phenotypes for gene: FOXL1 were changed from Otosclerosis 11 #MIM620576 to Otosclerosis 11 #MIM620576; Congenital heart disease, MONDO:0005453
Mendeliome v1.3675 Chirag Patel Added reviews for gene FOXL1 from panel Congenital Heart Defect
Mendeliome v1.3674 Chirag Patel Copied gene FMO5 from panel Congenital Heart Defect
Mendeliome v1.3674 FMO5 Chirag Patel gene: FMO5 was added
gene: FMO5 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: FMO5.
Mode of inheritance for gene: FMO5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FMO5 were set to Congenital heart disease, MONDO:0005453
Mendeliome v1.3673 Chirag Patel Added reviews for gene DTNA from panel Congenital Heart Defect
Mendeliome v1.3672 Chirag Patel Added reviews for gene DTNA from panel Congenital Heart Defect
Mendeliome v1.3671 CLIC2 Chirag Patel Tag disputed tag was added to gene: CLIC2.
Mendeliome v1.3671 Chirag Patel Copied gene EN2 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3671 EN2 Chirag Patel gene: EN2 was added
gene: EN2 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: EN2.
Mode of inheritance for gene: EN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EN2 were set to Complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3670 CNTN4 Chirag Patel Mode of inheritance for gene: CNTN4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3670 CNTN4 Chirag Patel Mode of inheritance for gene: CNTN4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3669 KIRREL3 Chirag Patel reviewed gene: KIRREL3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3669 KIRREL3 Chirag Patel Tag refuted was removed from gene: KIRREL3.
Tag disputed tag was added to gene: KIRREL3.
Mendeliome v1.3669 CNTN4 Chirag Patel Phenotypes for gene: CNTN4 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3669 CNTN4 Chirag Patel Phenotypes for gene: CNTN4 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3669 CNTN4 Chirag Patel Phenotypes for gene: CNTN4 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3669 CNTN4 Chirag Patel Phenotypes for gene: CNTN4 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3669 CNTN4 Chirag Patel Phenotypes for gene: CNTN4 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3669 CNTN4 Chirag Patel Phenotypes for gene: CNTN4 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3669 CNTN4 Chirag Patel Phenotypes for gene: CNTN4 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3668 CNTN4 Chirag Patel Phenotypes for gene: CNTN4 were changed from to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.3667 CNTN4 Chirag Patel Tag disputed tag was added to gene: CNTN4.
Mendeliome v1.3667 Chirag Patel Added reviews for gene CNTN4 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3666 CNTNAP5 Chirag Patel Marked gene: CNTNAP5 as ready
Mendeliome v1.3666 CNTNAP5 Chirag Patel Gene: cntnap5 has been classified as Red List (Low Evidence).
Mendeliome v1.3666 Chirag Patel Copied gene CNTNAP5 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3666 CNTNAP5 Chirag Patel gene: CNTNAP5 was added
gene: CNTNAP5 was added to Mendeliome. Sources: Expert Review Red,Genetic Health Queensland
disputed tags were added to gene: CNTNAP5.
Mode of inheritance for gene: CNTNAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNTNAP5 were set to 20346443
Phenotypes for gene: CNTNAP5 were set to Autism
Mendeliome v1.3665 TMLHE Chirag Patel Tag disputed tag was added to gene: TMLHE.
Mendeliome v1.3665 SLC9A9 Chirag Patel Tag disputed tag was added to gene: SLC9A9.
Mendeliome v1.3665 SLC6A4 Chirag Patel Phenotypes for gene: SLC6A4 were changed from Autism spectrum disorder MONDO:0005258 to Autism spectrum disorder MONDO:0005258
Mendeliome v1.3665 SLC6A4 Chirag Patel Phenotypes for gene: SLC6A4 were changed from {Obsessive-compulsive disorder}, MIM# 164230; depression; alcohol dependence to Autism spectrum disorder MONDO:0005258
Mendeliome v1.3664 SLC6A4 Chirag Patel Tag disputed tag was added to gene: SLC6A4.
Mendeliome v1.3664 SLC6A4 Chirag Patel commented on gene: SLC6A4: ClinGen DISPUTED - Jan 2021
Mendeliome v1.3664 SLC6A4 Chirag Patel reviewed gene: SLC6A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Autism spectrum disorder MONDO:0005258; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3664 COX4I1 Lucy Spencer Publications for gene: COX4I1 were set to 28766551; 22592081; 31290619
Mendeliome v1.3663 COX4I1 Lucy Spencer reviewed gene: COX4I1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28766551, 31290619, 40095452, 41203052; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 16 MIM#619060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3663 COQ5 Zornitza Stark Classified gene: COQ5 as Green List (high evidence)
Mendeliome v1.3663 COQ5 Zornitza Stark Gene: coq5 has been classified as Green List (High Evidence).
Mendeliome v1.3662 COQ5 Lucy Spencer Phenotypes for gene: COQ5 were changed from Coenzyme Q10 deficiency, primary 9, MIM#619028; Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability to Coenzyme Q10 deficiency, primary 9, MIM#619028
Mendeliome v1.3661 COQ5 Lucy Spencer Publications for gene: COQ5 were set to 29044765
Mendeliome v1.3660 COQ5 Lucy Spencer reviewed gene: COQ5: Rating: GREEN; Mode of pathogenicity: None; Publications: 29044765, 37599337, 21937992, 41199775, 36266294; Phenotypes: Coenzyme Q10 deficiency, primary, 9 MIM#619028; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3660 LAMB1 Zornitza Stark Phenotypes for gene: LAMB1 were changed from Lissencephaly 5, MIM# 615191; Cystic leukoencephalopathy; Adult-onset leukoencephalopathy to Lissencephaly 5, MIM# 615191; Leukoencephalopathy, adult-onset, MIM# 621424
Mendeliome v1.3659 LAMB1 Zornitza Stark edited their review of gene: LAMB1: Changed phenotypes: Lissencephaly 5, MIM# 615191, Leukoencephalopathy, adult-onset, MIM# 621424
Mendeliome v1.3659 FGD5 Sangavi Sivagnanasundram gene: FGD5 was added
gene: FGD5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FGD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGD5 were set to 32037394; 30232381
Phenotypes for gene: FGD5 were set to tetralogy of fallot MONDO:0008542
Review for gene: FGD5 was set to RED
Added comment: Appears to be two separate families reported with different nonsense variants in FGD5 associated with TOF. There is some author and recruitment overlap however there is no compelling evidence to state the two probands are related.

32037394 - one family reported with a nonsense variant in an individual with pulmonary stenosis and dysplastic valve, ASD - Glu322* (variant is absent in gnomAD v4.1)
30232381 (missed this publication) - individual reported with TOF, ASD, AF, hypertension, aortic dilation Arg1225* - present in gnomADv4.1 singleton in EAS population.

There is no clear evidence that LoF is the mechanism of disease. No pathogenic variants have been reported in ClinVar at this stage thus the gene should remain as Red till further evidence is provided.
Sources: Literature
Mendeliome v1.3658 CUL1 Zornitza Stark Marked gene: CUL1 as ready
Mendeliome v1.3658 CUL1 Zornitza Stark Gene: cul1 has been classified as Green List (High Evidence).
Mendeliome v1.3658 CUL1 Zornitza Stark Classified gene: CUL1 as Green List (high evidence)
Mendeliome v1.3658 CUL1 Zornitza Stark Gene: cul1 has been classified as Green List (High Evidence).
Mendeliome v1.3657 PDE11A Zornitza Stark Tag disputed was removed from gene: PDE11A.
Mendeliome v1.3657 KLF13 Krithika Murali Marked gene: KLF13 as ready
Mendeliome v1.3657 KLF13 Krithika Murali Gene: klf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3657 KLF13 Krithika Murali Classified gene: KLF13 as Amber List (moderate evidence)
Mendeliome v1.3657 KLF13 Krithika Murali Gene: klf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3656 KLF13 Krithika Murali gene: KLF13 was added
gene: KLF13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLF13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KLF13 were set to Congenital heart disease MONDO:0005453 - KLF13-related; Dilated cardiomyopathy - MONDO:0005021, KLF13-related
Review for gene: KLF13 was set to AMBER
Added comment: Curated by ClinGen as Moderate for association with congenital heart disease (12/2/2024)

PMID: 33215447 Wang et al 2020 - novel heterozygous variation, NM_015995.3: c.370G>T; p.(Glu124*), co-segregating with congenital heart disease in a 3-generation Chinese family. Supportive functional evidence.

PMID: 35369534 Abhinav et al 2022 - NM_015995.3: c.430G>T; p.(Glu144*) co-segregated with congenital heart disease in a Han Chinese family. Supportive functional evidence.

PMID: 32293321 Li et al 2020 - Two heterozygous missense variants in two unrelated patients with congenital heart disease. However, they have much higher gnomAD frequencies - c.487C > T (P163S) (11 hets gnomAD v4) and c.467G > A (S156N)(22 hets gnomAD v4). No segregation information and the functional evidence was not convincing. This paper was included as genetic evidence in the ClinGen curation.

Monoallelic variants have also been reported in association with adult-onset DCM.

PMID 36346048 Guo et al 2022 – Identified heterozygous KLF13 gene variants co-segregating with adult-onset DCM in 3 unrelated families - c.430G>T (p.E144X); c.580G>T (p.E194X) and c.595T>C (p.C199R). Functional studies support disrupted synergistic transactivation between mutant KLF13 and target genes ACTC1, MYH7 and GATA4. Monoallelic variants in KLF13 have also been associated with congenital heart disease. Of note, 2 individuals from Family 1 and 1 individual from Family 2 also had an atrial septal defect.

PMID 41201692 Tang et al 2025 – report a novel heterozygous truncating KLF13 mutation, i.e., NM_015995.3:c.534 C>G;p.(Tyr178) in two unrelated patients with adult onset DCM (42-year-old male patient and a 51-year old female case 51 years old). Variant was absent in healthy controls. No segregation evidence. Supportive functional evidence.

More evidence including segregation information, genotype-phenotype correlation between DCM and/or congenital heart disease and ascertainment from diverse ancestries required.
Sources: Literature
Mendeliome v1.3655 CUL1 Sarah Milton gene: CUL1 was added
gene: CUL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CUL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUL1 were set to PMID: 41189326
Phenotypes for gene: CUL1 were set to Neurodevelopmental disorder, MONDO:0700092, CUL1-related
Review for gene: CUL1 was set to GREEN
Added comment: CUL1 encodes Cullin 1 and is part of the SCF ubiquitin ligase complex which is involved in protein degradation and cell cycle progression.

Other Cullin proteins have previously been implicated in neurodevelopmental disorders e.g. CUL3

PMID: 41189326 describes 4 probands with microcephaly (postnatal in 3 out of 4), severe ID, seizures (2/4) and variable dysmorphic features. Variant types include nonsense, missense and splice with proposed LOF mechanism.
One individual inherited the variant from an affected mother with a slightly milder phenotype.
All variants were very rare (1 het) or absent from gnomAD v4.

CUL1 is under LOF constraint with very few NMD predicted variants in the population.

The paper described supportive zebrafish studies showing knockout models had reduced forebrain proportion and abnormal growth.
Sources: Literature
Mendeliome v1.3654 SEC31A Zornitza Stark Phenotypes for gene: SEC31A were changed from Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MIM# 618651; congenital neurodevelopmental syndrome; spastic paraplegia; multiple contractures; profound developmental delay; epilepsy; failure to thrive to Halperin-Birk syndrome, MIM# 618651
Mendeliome v1.3653 SEC31A Zornitza Stark Publications for gene: SEC31A were set to PMID: 30464055
Mendeliome v1.3652 Zornitza Stark Added reviews for gene SEC31A from panel Arthrogryposis
Mendeliome v1.3651 KCTD19 Zornitza Stark Marked gene: KCTD19 as ready
Mendeliome v1.3651 KCTD19 Zornitza Stark Gene: kctd19 has been classified as Green List (High Evidence).
Mendeliome v1.3651 Zornitza Stark Copied gene KCTD19 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.3651 KCTD19 Zornitza Stark gene: KCTD19 was added
gene: KCTD19 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: KCTD19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCTD19 were set to 37192818; 37485353; 39318590; 40410542; 41221840
Phenotypes for gene: KCTD19 were set to Infertility disorder, MONDO:0005047, KCTD19-related
Mendeliome v1.3650 MAFA Zornitza Stark Marked gene: MAFA as ready
Mendeliome v1.3650 MAFA Zornitza Stark Gene: mafa has been classified as Green List (High Evidence).
Mendeliome v1.3650 MAFA Zornitza Stark Classified gene: MAFA as Green List (high evidence)
Mendeliome v1.3650 MAFA Zornitza Stark Gene: mafa has been classified as Green List (High Evidence).
Mendeliome v1.3649 Zornitza Stark Added reviews for gene C1GALT1C1 from panel Atypical Haemolytic Uraemic Syndrome_MPGN
Mendeliome v1.3648 DHX38 Zornitza Stark Marked gene: DHX38 as ready
Mendeliome v1.3648 DHX38 Zornitza Stark Added comment: Comment when marking as ready: Maintain Amber rating after reviewing PMID 35719279, another homozygous ?synonymous variant with little supportive data.
Mendeliome v1.3648 DHX38 Zornitza Stark Gene: dhx38 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3648 DHX38 Zornitza Stark Publications for gene: DHX38 were set to 24737827; 30208423
Mendeliome v1.3647 ASIC5 Zornitza Stark Marked gene: ASIC5 as ready
Mendeliome v1.3647 ASIC5 Zornitza Stark Gene: asic5 has been classified as Red List (Low Evidence).
Mendeliome v1.3647 Zornitza Stark Copied gene ASIC5 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.3647 ASIC5 Zornitza Stark gene: ASIC5 was added
gene: ASIC5 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ASIC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASIC5 were set to PMID: 34395479
Phenotypes for gene: ASIC5 were set to Unexplained recurrent pregnancy loss
Mendeliome v1.3646 A4GALT Zornitza Stark Phenotypes for gene: A4GALT were changed from [Blood group, P1Pk system, p phenotype], MIM# 111400 to A4GALT-congenital disorder of glycosylation MONDO:0100587
Mendeliome v1.3645 A4GALT Zornitza Stark Publications for gene: A4GALT were set to
Mendeliome v1.3644 A4GALT Zornitza Stark Mode of inheritance for gene: A4GALT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3643 A4GALT Zornitza Stark Classified gene: A4GALT as Green List (high evidence)
Mendeliome v1.3643 A4GALT Zornitza Stark Gene: a4galt has been classified as Green List (High Evidence).
Mendeliome v1.3642 ZNF334 Zornitza Stark Marked gene: ZNF334 as ready
Mendeliome v1.3642 ZNF334 Zornitza Stark Gene: znf334 has been classified as Red List (Low Evidence).
Mendeliome v1.3642 GPKOW Zornitza Stark Publications for gene: GPKOW were set to 28612833; 40221893
Mendeliome v1.3641 GPKOW Zornitza Stark changed review comment from: Possible additional report in PMID 32426895, adult proband, extreme short stature and microcephaly, severe ID. De novo missense p.Gly427Arg.; to: Possible additional report in PMID 32426895, adult proband, extreme short stature and microcephaly, severe ID. De novo missense p.Gly427Arg.

MODERATE by ClinGen.
Mendeliome v1.3641 GPKOW Zornitza Stark reviewed gene: GPKOW: Rating: GREEN; Mode of pathogenicity: None; Publications: 32426895; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.3641 ARFGEF1 Zornitza Stark commented on gene: ARFGEF1: DEFINITIVE by ClinGen.
Mendeliome v1.3641 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from Cerebral Palsy MONDO#0006497, COL4A2-related; Brain small vessel disease 2 MIM# 614483 to Cerebral Palsy MONDO#0006497, COL4A2-related; Brain small vessel disease 2A, autosomal dominant MIM# 614483; Brain small vessel disease 2B, autosomal recessive, MIM# 621414
Mendeliome v1.3640 COL4A2 Zornitza Stark reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease 2B, autosomal recessive, MIM# 621414; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3640 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from GM1 gangliosidosis MONDO:0018149; GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010 to GM1 gangliosidosis MONDO:0018149; Mucopolysaccharidosis type IVB (Morquio) MIM#253010
Mendeliome v1.3639 GBE1 Zornitza Stark Phenotypes for gene: GBE1 were changed from Glycogen storage disease due to glycogen branching enzyme deficiency MONDO:0009292; Glycogen storage disease IV, MIM# 232500; Polyglucosan body disease, adult form MIM#263570 to Glycogen storage disease due to glycogen branching enzyme deficiency MONDO:0009292
Mendeliome v1.3638 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes MONDO:0100540; Pancreatic agenesis and congenital heart defects, 600001; Atrial septal defect 9, 614475; Atrioventricular septal defect 5, 614474; Tetralogy of Fallot, 187500; Persistent truncus arteriosus, 217095 to GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes MONDO:0100540
Mendeliome v1.3637 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from Structural congenital heart disease, multiple types - GATA4 MONDO:0100009; Atrial septal defect 2 MIM#607941; Atrioventricular septal defect 4 MIM#614430; Ventricular septal defect 1 MIM#614429 to Structural congenital heart disease, multiple types - GATA4 MONDO:0100009
Mendeliome v1.3636 GATA2 Zornitza Stark Phenotypes for gene: GATA2 were changed from Immunodeficiency 21, MIM# 614172; GATA2 deficiency with susceptibility to MDS/AML MONDO:0042982; Emberger syndrome, MIM# 614038; Deafness-lymphoedema-leukaemia syndrome MONDO:0013540 to GATA2 deficiency with susceptibility to MDS/AML MONDO:0042982
Mendeliome v1.3635 GLS Lucy Spencer Phenotypes for gene: GLS were changed from Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412; Cataract to Epileptic encephalopathy, early infantile, 71, MIM#618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM#618412; CASGID syndrome MIM#618339
Mendeliome v1.3634 GLS Lucy Spencer reviewed gene: GLS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: CASGID syndrome MIM#618339; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3634 GLI1 Lucy Spencer Phenotypes for gene: GLI1 were changed from Polydactyly, postaxial, type A8 MIM#618123; Polydactyly, preaxial I MIM#174400 to Postaxial polydactyly MONDO:0020927, GLI1-related; Polydactyly, postaxial, type A8 MIM#618123; Polydactyly, preaxial I MIM#174400
Mendeliome v1.3633 GLI1 Lucy Spencer reviewed gene: GLI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Postaxial polydactyly MONDO:0020927, GLI1-related; Mode of inheritance: None
Mendeliome v1.3633 CACNA1A Zornitza Stark Phenotypes for gene: CACNA1A were changed from Episodic ataxia, type 2 MIM#108500 to Developmental and epileptic encephalopathy 42, MIM# 617106
Mendeliome v1.3632 GLB1 Lucy Spencer Phenotypes for gene: GLB1 were changed from GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010 to GM1 gangliosidosis MONDO:0018149; GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010
Mendeliome v1.3631 GLB1 Lucy Spencer reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GM1 gangliosidosis MONDO:0018149; Mode of inheritance: None
Mendeliome v1.3631 GJC2 Lucy Spencer commented on gene: GJC2
Mendeliome v1.3631 GBE1 Lucy Spencer Phenotypes for gene: GBE1 were changed from Glycogen storage disease IV, MIM# 232500; Polyglucosan body disease, adult form MIM#263570 to Glycogen storage disease due to glycogen branching enzyme deficiency MONDO:0009292; Glycogen storage disease IV, MIM# 232500; Polyglucosan body disease, adult form MIM#263570
Mendeliome v1.3630 GBE1 Lucy Spencer reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease due to glycogen branching enzyme deficiency MONDO:0009292; Mode of inheritance: None
Mendeliome v1.3630 GATA6 Lucy Spencer Phenotypes for gene: GATA6 were changed from Pancreatic agenesis and congenital heart defects, 600001; Atrial septal defect 9, 614475; Atrioventricular septal defect 5, 614474; Tetralogy of Fallot, 187500; Persistent truncus arteriosus, 217095 to GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes MONDO:0100540; Pancreatic agenesis and congenital heart defects, 600001; Atrial septal defect 9, 614475; Atrioventricular septal defect 5, 614474; Tetralogy of Fallot, 187500; Persistent truncus arteriosus, 217095
Mendeliome v1.3629 GATA6 Lucy Spencer reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes MONDO:0100540; Mode of inheritance: None
Mendeliome v1.3629 GATA4 Lucy Spencer Phenotypes for gene: GATA4 were changed from Atrial septal defect 2 MIM#607941; Atrioventricular septal defect 4 MIM#614430; Ventricular septal defect 1 MIM#614429 to Structural congenital heart disease, multiple types - GATA4 MONDO:0100009; Atrial septal defect 2 MIM#607941; Atrioventricular septal defect 4 MIM#614430; Ventricular septal defect 1 MIM#614429
Mendeliome v1.3628 GATA4 Lucy Spencer reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Structural congenital heart disease, multiple types - GATA4 MONDO:0100009; Mode of inheritance: None
Mendeliome v1.3628 GATA2 Lucy Spencer reviewed gene: GATA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GATA2 deficiency with susceptibility to MDS/AML MONDO:0042982; Mode of inheritance: None
Mendeliome v1.3628 GAD1 Lucy Spencer Phenotypes for gene: GAD1 were changed from Cerebral palsy, spastic quadriplegic, 1, MIM#603513; Developmental and epileptic encephalopathy 89, MIM# 619124 to Developmental and epileptic encephalopathy 89, MIM# 619124
Mendeliome v1.3627 GAD1 Lucy Spencer commented on gene: GAD1
Mendeliome v1.3627 CACNA1A Zornitza Stark Mode of inheritance for gene: CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3626 CACNA1A Zornitza Stark reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476654, 36063114; Phenotypes: Developmental and epileptic encephalopathy 42, MIM# 617106; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3626 EXOSC10 Zornitza Stark Marked gene: EXOSC10 as ready
Mendeliome v1.3626 EXOSC10 Zornitza Stark Gene: exosc10 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3626 EXOSC10 Zornitza Stark Classified gene: EXOSC10 as Amber List (moderate evidence)
Mendeliome v1.3626 EXOSC10 Zornitza Stark Gene: exosc10 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3625 Bryony Thompson Copied gene SPP2 from panel Retinitis pigmentosa_Autosomal Dominant
Mendeliome v1.3625 SPP2 Bryony Thompson gene: SPP2 was added
gene: SPP2 was added to Mendeliome. Sources: Expert Review Red,Royal Melbourne Hospital
Mode of inheritance for gene: SPP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPP2 were set to 26459573
Phenotypes for gene: SPP2 were set to Autosomal dominant retinitis pigmentosa
Mendeliome v1.3624 Bryony Thompson Added reviews for gene CRB1 from panel Retinitis pigmentosa_Autosomal Dominant
Mendeliome v1.3623 PCSK5 Chirag Patel Marked gene: PCSK5 as ready
Mendeliome v1.3623 PCSK5 Chirag Patel Gene: pcsk5 has been classified as Red List (Low Evidence).
Mendeliome v1.3623 Chirag Patel Copied gene PCSK5 from panel Congenital Heart Defect
Mendeliome v1.3623 PCSK5 Chirag Patel gene: PCSK5 was added
gene: PCSK5 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: PCSK5.
Mode of inheritance for gene: PCSK5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PCSK5 were set to Syndromic congenital heart disease, MONDO:0100614
Mendeliome v1.3622 SCN2B Chirag Patel Marked gene: SCN2B as ready
Mendeliome v1.3622 SCN2B Chirag Patel Gene: scn2b has been classified as Red List (Low Evidence).
Mendeliome v1.3622 SCN2B Chirag Patel Marked gene: SCN2B as ready
Mendeliome v1.3622 SCN2B Chirag Patel Gene: scn2b has been classified as Red List (Low Evidence).
Mendeliome v1.3622 SLMAP Chirag Patel Marked gene: SLMAP as ready
Mendeliome v1.3622 SLMAP Chirag Patel Gene: slmap has been classified as Red List (Low Evidence).
Mendeliome v1.3622 Chirag Patel Copied gene SCN2B from panel Brugada syndrome
Mendeliome v1.3622 SCN2B Chirag Patel gene: SCN2B was added
gene: SCN2B was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: SCN2B.
Mode of inheritance for gene: SCN2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SCN2B were set to Brugada syndrome, MONDO:0015263
Mendeliome v1.3621 Chirag Patel Copied gene SLMAP from panel Brugada syndrome
Mendeliome v1.3621 SLMAP Chirag Patel gene: SLMAP was added
gene: SLMAP was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: SLMAP.
Mode of inheritance for gene: SLMAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLMAP were set to Brugada syndrome, MONDO:0015263
Mendeliome v1.3620 KCNE5 Chirag Patel Tag disputed tag was added to gene: KCNE5.
Mendeliome v1.3620 KCNE5 Chirag Patel Phenotypes for gene: KCNE5 were changed from Atrial fibrillation to Atrial fibrillation; Brugada syndrome, MONDO:0015263
Mendeliome v1.3619 Chirag Patel Added reviews for gene KCNE5 from panel Brugada syndrome
Mendeliome v1.3618 PLAT Chirag Patel Marked gene: PLAT as ready
Mendeliome v1.3618 PLAT Chirag Patel Gene: plat has been classified as Red List (Low Evidence).
Mendeliome v1.3618 TP53BP2 Chirag Patel Marked gene: TP53BP2 as ready
Mendeliome v1.3618 TP53BP2 Chirag Patel Gene: tp53bp2 has been classified as Red List (Low Evidence).
Mendeliome v1.3618 TP53BP2 Chirag Patel gene: TP53BP2 was added
gene: TP53BP2 was added to Mendeliome. Sources: ClinGen
disputed tags were added to gene: TP53BP2.
Mode of inheritance for gene: TP53BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53BP2 were set to Open-angle glaucoma MONDO:0005338
Review for gene: TP53BP2 was set to RED
Added comment: ClinGen DISPUTED - May 2023
Sources: ClinGen
Mendeliome v1.3617 Chirag Patel Copied gene PLAT from panel Bleeding and Platelet Disorders
Mendeliome v1.3617 PLAT Chirag Patel gene: PLAT was added
gene: PLAT was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: PLAT.
Mode of inheritance for gene: PLAT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PLAT were set to Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872
Mendeliome v1.3616 ACADL Chirag Patel Phenotypes for gene: ACADL were changed from Hereditary pulmonary alveoral proteinosis, MONDO:0012580, ACADL-related to Long chain acyl-CoA dehydrogenase deficiency MONDO:0020531
Mendeliome v1.3615 Chirag Patel Added reviews for gene ACADL from panel Fatty Acid Oxidation Defects
Mendeliome v1.3614 STEAP3 Chirag Patel Phenotypes for gene: STEAP3 were changed from Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094 to Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094
Mendeliome v1.3614 STEAP3 Chirag Patel Phenotypes for gene: STEAP3 were changed from Anaemia, hypochromic microcytic, with iron overload 2, MIM# 615234 to Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094
Mendeliome v1.3613 STEAP3 Chirag Patel Tag disputed tag was added to gene: STEAP3.
Mendeliome v1.3613 Chirag Patel Added reviews for gene STEAP3 from panel Metal Metabolism Disorders
Mendeliome v1.3612 FOXD3 Chirag Patel Phenotypes for gene: FOXD3 were changed from Autoimmune disease, susceptibility to, 1 MONDO:0011919 to Autoimmune disease, susceptibility to, 1 MONDO:0011919; Aniridia, MONDO:0019172
Mendeliome v1.3611 FOXD3 Chirag Patel Deleted their review
Mendeliome v1.3611 Chirag Patel Added reviews for gene FOXD3 from panel Eye Anterior Segment Abnormalities
Mendeliome v1.3610 Chirag Patel Added reviews for gene PRKACG from panel Bleeding and Platelet Disorders
Mendeliome v1.3609 PRKACG Chirag Patel Tag disputed tag was added to gene: PRKACG.
Mendeliome v1.3609 MYOZ2 Chirag Patel Phenotypes for gene: MYOZ2 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.3609 MYOZ2 Chirag Patel Phenotypes for gene: MYOZ2 were changed from Cardiomyopathy, hypertrophic, 16 MIM#613838 to Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.3608 MYOZ2 Chirag Patel Tag disputed tag was added to gene: MYOZ2.
Mendeliome v1.3608 Chirag Patel Added reviews for gene MYOZ2 from panel Hypertrophic cardiomyopathy_HCM
Mendeliome v1.3607 MYOM1 Chirag Patel Tag disputed tag was added to gene: MYOM1.
Mendeliome v1.3607 Chirag Patel Added reviews for gene MYOM1 from panel Hypertrophic cardiomyopathy_HCM
Mendeliome v1.3606 MYLK2 Chirag Patel Tag disputed tag was added to gene: MYLK2.
Mendeliome v1.3606 Chirag Patel Added reviews for gene MYLK2 from panel Hypertrophic cardiomyopathy_HCM
Mendeliome v1.3605 CALR3 Chirag Patel Phenotypes for gene: CALR3 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.3604 CALR3 Chirag Patel Tag refuted was removed from gene: CALR3.
Tag disputed tag was added to gene: CALR3.
Mendeliome v1.3604 Chirag Patel Added reviews for gene CALR3 from panel Hypertrophic cardiomyopathy_HCM
Mendeliome v1.3603 ANKRD1 Chirag Patel Tag disputed tag was added to gene: ANKRD1.
Mendeliome v1.3603 ANKRD1 Chirag Patel reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: None
Mendeliome v1.3603 Chirag Patel Copied gene KCNE2 from panel Long QT Syndrome
Mendeliome v1.3603 KCNE2 Chirag Patel gene: KCNE2 was added
gene: KCNE2 was added to Mendeliome. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: KCNE2.
Mode of inheritance for gene: KCNE2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNE2 were set to 31983240; 28794082
Phenotypes for gene: KCNE2 were set to Long QT syndrome
Mendeliome v1.3602 Chirag Patel Copied gene AKAP9 from panel Long QT Syndrome
Mendeliome v1.3602 AKAP9 Chirag Patel gene: AKAP9 was added
gene: AKAP9 was added to Mendeliome. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: AKAP9.
Mode of inheritance for gene: AKAP9 was set to Unknown
Publications for gene: AKAP9 were set to 31983240
Phenotypes for gene: AKAP9 were set to long QT syndrome
Mendeliome v1.3601 TUBA8 Chirag Patel Deleted their review
Mendeliome v1.3601 TUBA8 Chirag Patel Deleted their comment
Mendeliome v1.3601 Chirag Patel Added reviews for gene TUBA8 from panel Polymicrogyria and Schizencephaly
Mendeliome v1.3600 Chirag Patel Copied gene TEKT1 from panel Ciliary Dyskinesia
Mendeliome v1.3600 TEKT1 Chirag Patel gene: TEKT1 was added
gene: TEKT1 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: TEKT1.
Mode of inheritance for gene: TEKT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TEKT1 were set to Primary ciliary dyskinesia, MONDO:0016575
Mendeliome v1.3599 DNAH14 Chirag Patel changed review comment from: ClinGen DISPUTED - May 2025
Sources: ClinGen; to: PCD - ClinGen DISPUTED - May 2025
Sources: ClinGen
Mendeliome v1.3599 Chirag Patel Added reviews for gene DNAH14 from panel Ciliary Dyskinesia
Mendeliome v1.3598 AK7 Chirag Patel Marked gene: AK7 as ready
Mendeliome v1.3598 AK7 Chirag Patel Gene: ak7 has been classified as Red List (Low Evidence).
Mendeliome v1.3598 Chirag Patel Copied gene AK7 from panel Ciliary Dyskinesia
Mendeliome v1.3598 AK7 Chirag Patel gene: AK7 was added
gene: AK7 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: AK7.
Mode of inheritance for gene: AK7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AK7 were set to Primary ciliary dyskinesia, MONDO:0016575
Mendeliome v1.3597 IGBP1 Chirag Patel Tag disputed tag was added to gene: IGBP1.
Mendeliome v1.3597 IGBP1 Chirag Patel reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3597 ARHGEF6 Chirag Patel Tag disputed tag was added to gene: ARHGEF6.
Mendeliome v1.3597 Chirag Patel Added reviews for gene ARHGEF6 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3596 ANK2 Chirag Patel changed review comment from: ClinGen DISPUTED for catecholaminergic polymorphic ventricular tachycardia - Jan 2021
Sources: ClinGen; to: CPVT - ClinGen DISPUTED - Jan 2021
Sources: ClinGen
Mendeliome v1.3596 PKP2 Chirag Patel edited their review of gene: PKP2: Added comment: CPVT - ClinGen DISPUTED - Jan 2021; Changed phenotypes: Catecholaminergic polymorphic ventricular tachycardia, MONDO:0017990
Mendeliome v1.3596 ANK2 Chirag Patel changed review comment from: ClinGen DISPUTED - Jan 2021
Sources: ClinGen; to: ClinGen DISPUTED for catecholaminergic polymorphic ventricular tachycardia - Jan 2021
Sources: ClinGen
Mendeliome v1.3596 Chirag Patel Added reviews for gene ANK2 from panel Catecholaminergic Polymorphic Ventricular Tachycardia
Mendeliome v1.3595 Chirag Patel Added reviews for gene PKP2 from panel Catecholaminergic Polymorphic Ventricular Tachycardia
Mendeliome v1.3594 EWSR1 Chirag Patel Tag disputed tag was added to gene: EWSR1.
Mendeliome v1.3594 UPK3A Chirag Patel commented on gene: UPK3A: ClinGen DISPUTED - Jan 2023
Mendeliome v1.3594 UPK3A Chirag Patel Phenotypes for gene: UPK3A were changed from CAKUT to Congenital anomaly of kidney and urinary tract, MONDO:0019719
Mendeliome v1.3593 UPK3A Chirag Patel Tag disputed tag was added to gene: UPK3A.
Mendeliome v1.3593 Chirag Patel Added reviews for gene UPK3A from panel Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic
Mendeliome v1.3592 Chirag Patel Added reviews for gene ZFYVE27 from panel Hereditary Spastic Paraplegia - adult onset
Mendeliome v1.3591 ZFYVE27 Chirag Patel Tag disputed tag was added to gene: ZFYVE27.
Mendeliome v1.3590 PIK3R5 Chirag Patel Tag disputed tag was added to gene: PIK3R5.
Mendeliome v1.3591 Chirag Patel Added reviews for gene PIK3R5 from panel Cerebellar and Pontocerebellar Hypoplasia
Mendeliome v1.3590 CFAP47 Chirag Patel changed review comment from: 3 Japanese individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts, infertility, or any family history of cystic kidney disease. WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased. CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.; to: 3 Japanese individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts, infertility, or any family history of cystic kidney disease. WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased. CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.

ClinGen DISPUTED - Feb 2025
Mendeliome v1.3590 MYO1F Chirag Patel Marked gene: MYO1F as ready
Mendeliome v1.3590 MYO1F Chirag Patel Gene: myo1f has been classified as Red List (Low Evidence).
Mendeliome v1.3590 MYO1F Chirag Patel gene: MYO1F was added
gene: MYO1F was added to Mendeliome. Sources: ClinGen
disputed tags were added to gene: MYO1F.
Mode of inheritance for gene: MYO1F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYO1F were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Review for gene: MYO1F was set to RED
Added comment: ClinGen DISPUTED - Oct 2024
Sources: ClinGen
Mendeliome v1.3589 CEMIP Chirag Patel Marked gene: CEMIP as ready
Mendeliome v1.3589 CEMIP Chirag Patel Gene: cemip has been classified as Red List (Low Evidence).
Mendeliome v1.3589 Chirag Patel Copied gene CEMIP from panel Deafness_IsolatedAndComplex
Mendeliome v1.3589 CEMIP Chirag Patel gene: CEMIP was added
gene: CEMIP was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: CEMIP.
Mode of inheritance for gene: CEMIP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEMIP were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Mendeliome v1.3588 MYO1C Chirag Patel Marked gene: MYO1C as ready
Mendeliome v1.3588 MYO1C Chirag Patel Gene: myo1c has been classified as Red List (Low Evidence).
Mendeliome v1.3588 Chirag Patel Copied gene MYO1C from panel Deafness_IsolatedAndComplex
Mendeliome v1.3588 MYO1C Chirag Patel gene: MYO1C was added
gene: MYO1C was added to Mendeliome. Sources: ClinGen
disputed tags were added to gene: MYO1C.
Mode of inheritance for gene: MYO1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYO1C were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Mendeliome v1.3587 PDLIM3 Chirag Patel Tag disputed tag was added to gene: PDLIM3.
Mendeliome v1.3587 PDLIM3 Chirag Patel Phenotypes for gene: PDLIM3 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy; Dilated cardiomyopathy, MONDO:0005021
Mendeliome v1.3586 Chirag Patel Added reviews for gene PDLIM3 from panel Dilated Cardiomyopathy
Mendeliome v1.3585 Chirag Patel Copied gene PKP2 from panel Dilated Cardiomyopathy
Mendeliome v1.3585 PKP2 Chirag Patel gene: PKP2 was added
gene: PKP2 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PKP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKP2 were set to 15489853; 16567567; 30562116; 35059364; 38050058
Phenotypes for gene: PKP2 were set to Arrhythmogenic right ventricular dysplasia 9 (MIM#609040); Dilated cardiomyopathy, MONDO:0005021, PKP2-related; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Mendeliome v1.3584 PRICKLE1 Chirag Patel Tag disputed tag was added to gene: PRICKLE1.
Mendeliome v1.3584 CPA6 Chirag Patel Source Victorian Clinical Genetics Services was removed from CPA6.
Source ClinGen was added to CPA6.
Mode of inheritance for gene CPA6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3583 FAAP24 Chirag Patel Tag disputed tag was added to gene: FAAP24.
Mendeliome v1.3583 FAAP24 Chirag Patel reviewed gene: FAAP24: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3583 LIMS2 Chirag Patel Tag disputed tag was added to gene: LIMS2.
Mendeliome v1.3583 Chirag Patel Added reviews for gene LIMS2 from panel Myopathy - paediatric onset
Mendeliome v1.3582 TMPO Chirag Patel Tag refuted tag was added to gene: TMPO.
Mendeliome v1.3582 SRPX2 Chirag Patel reviewed gene: SRPX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3582 SRPX2 Chirag Patel Tag refuted tag was added to gene: SRPX2.
Mendeliome v1.3582 Chirag Patel Copied gene RANGRF from panel Brugada syndrome
Mendeliome v1.3582 RANGRF Chirag Patel gene: RANGRF was added
gene: RANGRF was added to Mendeliome. Sources: Expert Review Red,ClinGen
refuted tags were added to gene: RANGRF.
Mode of inheritance for gene: RANGRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RANGRF were set to Brugada syndrome, MONDO:0015263
Mendeliome v1.3581 Chirag Patel Copied gene RAB40AL from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3581 RAB40AL Chirag Patel gene: RAB40AL was added
gene: RAB40AL was added to Mendeliome. Sources: Expert Review Red,Genetic Health Queensland
refuted tags were added to gene: RAB40AL.
Mode of inheritance for gene: RAB40AL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RAB40AL were set to 25044830
Phenotypes for gene: RAB40AL were set to MENTAL RETARDATION, X-LINKED, SYNDROMIC, MARTIN-PROBST TYPE
Mendeliome v1.3580 MYO1A Chirag Patel Classified gene: MYO1A as Red List (low evidence)
Mendeliome v1.3580 MYO1A Chirag Patel Gene: myo1a has been classified as Red List (Low Evidence).
Mendeliome v1.3579 MYO1A Chirag Patel reviewed gene: MYO1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital diarrhea, MONDO:0000824; Mode of inheritance: None
Mendeliome v1.3579 KLF11 Chirag Patel Tag refuted tag was added to gene: KLF11.
Mendeliome v1.3579 GEN1 Chirag Patel Marked gene: GEN1 as ready
Mendeliome v1.3579 GEN1 Chirag Patel Gene: gen1 has been classified as Red List (Low Evidence).
Mendeliome v1.3579 Chirag Patel Copied gene GEN1 from panel Breast Cancer
Mendeliome v1.3579 GEN1 Chirag Patel gene: GEN1 was added
gene: GEN1 was added to Mendeliome. Sources: ClinGen
refuted tags were added to gene: GEN1.
Mode of inheritance for gene: GEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GEN1 were set to Hereditary breast carcinoma, MONDO:0016419
Mendeliome v1.3578 EFHC1 Chirag Patel commented on gene: EFHC1
Mendeliome v1.3578 EFHC1 Chirag Patel Tag disputed was removed from gene: EFHC1.
Tag refuted tag was added to gene: EFHC1.
Mendeliome v1.3578 CHRNA7 Chirag Patel Tag refuted tag was added to gene: CHRNA7.
Mendeliome v1.3578 CRH Chirag Patel Marked gene: CRH as ready
Mendeliome v1.3578 CRH Chirag Patel Gene: crh has been classified as Red List (Low Evidence).
Mendeliome v1.3578 Chirag Patel Copied gene CRH from panel Genetic Epilepsy
Mendeliome v1.3578 CRH Chirag Patel gene: CRH was added
gene: CRH was added to Mendeliome. Sources: Expert Review Red,ClinGen
refuted tags were added to gene: CRH.
Mode of inheritance for gene: CRH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRH were set to Epilepsy, MONDO:0005027
Mendeliome v1.3577 ADRA2B Chirag Patel Tag refuted tag was added to gene: ADRA2B.
Mendeliome v1.3577 EXOSC10 Rylee Peters changed review comment from: PMID: 41132091 | Article describes four unrelated individuals with heterozygous de novo EXOSC10 variants (1x missense and 4x microdeletions within the 1p36 region) presenting with primary microcephaly, anomalies of cortical structures, intellectual disability and global developmental delay. Exosc10 heterozygous knockout mice exhibited reduced cortical size resembling microcephaly, with a more severe phenotype observed in homozygous knockout mice.

However, these microdeletions occur within the 1p36 region, which is associated with chromosome 1p36 deletion syndrome (green in panelapp), and encompass many genes.
Sources: Literature; to: PMID: 41132091 | Article describes four unrelated individuals with heterozygous de novo EXOSC10 variants (1x missense and 4x microdeletions within the 1p36 region) presenting with primary microcephaly, anomalies of cortical structures, intellectual disability and global developmental delay. Exosc10 heterozygous knockout mice exhibited reduced cortical size resembling microcephaly, with a more severe phenotype observed in homozygous knockout mice.

However, these microdeletions occur within the 1p36 region, which is associated with chromosome 1p36 deletion syndrome (green in Panelapp), and encompass many genes.
Sources: Literature
Mendeliome v1.3577 EXOSC10 Rylee Peters gene: EXOSC10 was added
gene: EXOSC10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOSC10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EXOSC10 were set to 41132091
Phenotypes for gene: EXOSC10 were set to Microcephaly, MONDO:0001149, EXOSC10-related
Review for gene: EXOSC10 was set to AMBER
Added comment: PMID: 41132091 | Article describes four unrelated individuals with heterozygous de novo EXOSC10 variants (1x missense and 4x microdeletions within the 1p36 region) presenting with primary microcephaly, anomalies of cortical structures, intellectual disability and global developmental delay. Exosc10 heterozygous knockout mice exhibited reduced cortical size resembling microcephaly, with a more severe phenotype observed in homozygous knockout mice.

However, these microdeletions occur within the 1p36 region, which is associated with chromosome 1p36 deletion syndrome (green in panelapp), and encompass many genes.
Sources: Literature
Mendeliome v1.3576 RPS6KC1 Zornitza Stark Marked gene: RPS6KC1 as ready
Mendeliome v1.3576 RPS6KC1 Zornitza Stark Gene: rps6kc1 has been classified as Green List (High Evidence).
Mendeliome v1.3576 STARD9 Zornitza Stark Marked gene: STARD9 as ready
Mendeliome v1.3576 STARD9 Zornitza Stark Gene: stard9 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3576 STARD9 Rylee Peters Classified gene: STARD9 as Amber List (moderate evidence)
Mendeliome v1.3576 STARD9 Rylee Peters Gene: stard9 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3575 RPS6KC1 Rylee Peters Classified gene: RPS6KC1 as Green List (high evidence)
Mendeliome v1.3575 RPS6KC1 Rylee Peters Gene: rps6kc1 has been classified as Green List (High Evidence).
Mendeliome v1.3574 RPS6KC1 Rylee Peters gene: RPS6KC1 was added
gene: RPS6KC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPS6KC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPS6KC1 were set to 41130203
Phenotypes for gene: RPS6KC1 were set to Complex neurodevelopmental disorder, MONDO:0100038, RPS6KC1-related
Review for gene: RPS6KC1 was set to GREEN
Added comment: PMID: 41130203 | Bi-allelic RPS6KC1 variants identified in 13 individuals from 8 independent families. Phenotypic manifestations included neurodevelopmental delay, epilepsy, hypotonia, spastic paraplegia, brain white matter loss, and dysmorphic features.
Functional studies including a HAP1 cellular model and a Drosophila melanogaster model recapitulated the defects observed in individuals with RPS6KC1 variants.
Sources: Literature
Mendeliome v1.3573 DOCK4 Zornitza Stark Phenotypes for gene: DOCK4 were changed from DOCK4-related neurodevelopmental disorder (MONDO:0060490) to Neurodevelopmental disorder, MONDO:0700092, DOCK4-related
Mendeliome v1.3572 DOCK4 Zornitza Stark reviewed gene: DOCK4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, DOCK4-related; Mode of inheritance: None
Mendeliome v1.3572 STARD9 Rylee Peters gene: STARD9 was added
gene: STARD9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: STARD9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STARD9 were set to 41137852; 28777490
Phenotypes for gene: STARD9 were set to Syndromic disorder (MONDO:0002254), STARD9-related
Review for gene: STARD9 was set to AMBER
Added comment: STARD9 enables microtubule binding activity, motor activity and is involved in spindle assembly.

PMID: 41137852 | 1x cHet individual with early-onset febrile seizures followed by atypical absence seizures. The two missense identified, p.(Leu694Phe) and p.(Met3409Val), have 5 hets and 125 hets respectively in gnomAD v4.

PMID: 28777490 | 1x hom individual with a frameshift variant, p.(L3920fs*38). Patient had severe intellectual disability, epilepsy, dysmorphic features, acquired microcephaly, and blindness. Patient cells showed mitotic spindle assembly defects.
Sources: Literature
Mendeliome v1.3571 LRRC7 Zornitza Stark Phenotypes for gene: LRRC7 were changed from neurodevelopmental disorder (MONDO:0700092), LRRC7-related to Intellectual developmental disorder, autosomal dominant 77, MIM# 621415
Mendeliome v1.3570 LRRC7 Zornitza Stark edited their review of gene: LRRC7: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 77, MIM# 621415
Mendeliome v1.3570 PEX11B Zornitza Stark changed review comment from: Comment when marking as ready: Two published families and one International.; to: Comment when marking as ready: Two published families and one internal.
Mendeliome v1.3570 KLHL13 Krithika Murali Phenotypes for gene: KLHL13 were changed from HMSN to Neurodevelopmental disorder, MONDO:0700092, KLHL13-related
Mendeliome v1.3569 KLHL13 Krithika Murali Publications for gene: KLHL13 were set to 24627108
Mendeliome v1.3568 KLHL13 Krithika Murali Classified gene: KLHL13 as Green List (high evidence)
Mendeliome v1.3568 KLHL13 Krithika Murali Gene: klhl13 has been classified as Green List (High Evidence).
Mendeliome v1.3567 Krithika Murali Added reviews for gene KLHL13 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3566 NOL10 Zornitza Stark Marked gene: NOL10 as ready
Mendeliome v1.3566 NOL10 Zornitza Stark Gene: nol10 has been classified as Red List (Low Evidence).
Mendeliome v1.3566 CASP1 Zornitza Stark Phenotypes for gene: CASP1 were changed from Absent IL18 and lymphopenia but no clinical disease to Inborn error of immunity, MONDO:0003778, CASP1-related; Absent IL18 and lymphopenia but no clinical disease
Mendeliome v1.3565 UNC119 Zornitza Stark Publications for gene: UNC119 were set to 11006213; 23563732; 27079236; 22184408
Mendeliome v1.3564 UNC119 Zornitza Stark edited their review of gene: UNC119: Added comment: PMID 41107067: another mouse model to support the association with cone-rod dystrophy.; Changed publications: 22184408, 41107067
Mendeliome v1.3564 TXNIP Zornitza Stark Marked gene: TXNIP as ready
Mendeliome v1.3564 TXNIP Zornitza Stark Gene: txnip has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3564 HDAC6 Bryony Thompson Marked gene: HDAC6 as ready
Mendeliome v1.3564 HDAC6 Bryony Thompson Gene: hdac6 has been classified as Red List (Low Evidence).
Mendeliome v1.3564 HDAC6 Bryony Thompson gene: HDAC6 was added
gene: HDAC6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HDAC6 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: HDAC6 were set to 20181727
Phenotypes for gene: HDAC6 were set to chondrodysplasia MONDO:0022723
Review for gene: HDAC6 was set to RED
Added comment: PMID 20181727 reports eight individuals from a single unrelated family with X-linked dominant chondrodysplasia caused by a 3′‑UTR HDAC6 variant (c.*281A>T) that abolishes miR‑433 regulation, leading to HDAC6 overexpression; severe skeletal anomalies are seen in males and a milder asymmetric short‑limb phenotype in heterozygous females. Functional assays in MG63 cells and fetal tissues confirm loss of miRNA‑mediated repression.
Sources: Literature
Mendeliome v1.3563 NAA16 Zornitza Stark Marked gene: NAA16 as ready
Mendeliome v1.3563 NAA16 Zornitza Stark Gene: naa16 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3563 OAS2 Zornitza Stark Phenotypes for gene: OAS2 were changed from Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related to Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Mendeliome v1.3562 OAS2 Zornitza Stark edited their review of gene: OAS2: Changed phenotypes: Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Mendeliome v1.3562 BAIAP2 Bryony Thompson Marked gene: BAIAP2 as ready
Mendeliome v1.3562 BAIAP2 Bryony Thompson Gene: baiap2 has been classified as Green List (High Evidence).
Mendeliome v1.3562 BAIAP2 Bryony Thompson Classified gene: BAIAP2 as Green List (high evidence)
Mendeliome v1.3562 BAIAP2 Bryony Thompson Gene: baiap2 has been classified as Green List (High Evidence).
Mendeliome v1.3561 BAIAP2 Bryony Thompson gene: BAIAP2 was added
gene: BAIAP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAIAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAIAP2 were set to 41133935; 38149472
Phenotypes for gene: BAIAP2 were set to BAIAP2-related complex neurodevelopmental disorder MONDO:0100038
Review for gene: BAIAP2 was set to GREEN
Added comment: The protein encoded by this gene has been identified as a brain-specific angiogenesis inhibitor (BAI1)-binding protein.
6 individuals with de novo GoF missense variants with DEE. Only 1 individual reported with a LoF missense variant & lissencephaly.
PMID: 41133935 - Reports 6 individuals from 6 unrelated families with heterozygous de novo missense BAIAP2 variants presenting with developmental and epileptic encephalopathy (DEE). Core phenotype: infantile/early‑childhood onset refractory seizures, severe language and motor delay, intellectual disability. All patients have detailed clinical descriptions; variants cluster in the phosphorylation‑rich autoinhibited region. Functional assays (HeLa cell spreading, primary hippocampal neuron electrophysiology, zebrafish overexpression) demonstrate gain‑of‑function effects. No benign variants reported; variants absent from gnomAD.
PMID: 38149472 - Reports 1 individual from 1 family with a de novo heterozygous BAIAP2 missense variant p.Arg29Trp (4 hets in gnomAD v4.1) presenting with classical lissencephaly (posterior>anterior gradient), severe global developmental delay and refractory epilepsy. Mouse Baiap2 knockdown reproduces neuronal migration defects; the p.Arg29Trp variant fails to rescue and shows reduced membrane localization, indicating a loss‑of‑function effect.
Sources: Literature
Mendeliome v1.3560 TXNIP Lucy Spencer Classified gene: TXNIP as Amber List (moderate evidence)
Mendeliome v1.3560 TXNIP Lucy Spencer Gene: txnip has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3559 TXNIP Lucy Spencer gene: TXNIP was added
gene: TXNIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TXNIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNIP were set to 41116060; 30755400
Phenotypes for gene: TXNIP were set to Metabolic disease MONDO:0005066, TXNIP-related
Review for gene: TXNIP was set to AMBER
Added comment: TXNIP binds and inhibits TXN, controlling its activity. The TXN system is a major cellular system for control of redox state, antioxidant defense, and several signaling pathways. TXNIP can also activate the NLRP3 inflammasome and suppress of the activities of the
nuclear factor (erythroid-derived 2)–like 2 (Nrf2) transcription factor.

PMID 30755400 reports three affected siblings from a consanguineous Libyan family with autosomal recessive congenital lactic acidosis and low serum methionine. 2 of the three siblings have developed normally and appear to be mostly asymptomatic apart from variable hypoglycaemia, while the third had failure the thrive as an infant, slow development, ?autism, and slight muscular hypotonus. All three siblings were homozygous for TXNIP c.174_175delinsTT which creates a stopgain at p.Gly59* (and a missense at p.58). Patient‑derived fibroblasts and myoblasts show impaired pyruvate‑driven mitochondrial respiration that is rescued by TXNIP re‑constitution. However, patient cells showed no difference in cell growth or morphology, and had normal downstream TXN activity while Nrf2 target gene transcripts were upregulated.

PMID 41116060 describes an additional individual with a severe metabolic disease; lactic acidosis, recurrent hypoglycaemia, significant developmental delay, epileptic seizures, and hypotonia. Homozygous for c.642_643insT p.(Ile215Tyrfs*59). Functional studies showed it disrupts SLC7A5-SLC3A2 endocytosis and cellular glucose uptake.
Sources: Literature
Mendeliome v1.3558 ESRP2 Chirag Patel Classified gene: ESRP2 as Green List (high evidence)
Mendeliome v1.3558 ESRP2 Chirag Patel Gene: esrp2 has been classified as Green List (High Evidence).
Mendeliome v1.3557 Chirag Patel Added reviews for gene ESRP2 from panel Clefting disorders
Mendeliome v1.3556 NAA16 Lucy Spencer Classified gene: NAA16 as Amber List (moderate evidence)
Mendeliome v1.3556 NAA16 Lucy Spencer Gene: naa16 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3555 NAA16 Lucy Spencer gene: NAA16 was added
gene: NAA16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAA16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAA16 were set to 41148812; 23665959; 28991257
Phenotypes for gene: NAA16 were set to Congenital heart disease, MONDO:0005453, NAA16-related
Review for gene: NAA16 was set to AMBER
Added comment: NAA16 is part of the auxiliary subunit of the NatA complex along with NAA15. this complex is responsible for acetylating a broad range of proteins following initiator methionine removal. NAA15 and NAA10 which is part of the catalytic subunit of the complex have previously been associated with neurodevelopmental disorders, including CHD for NAA15.

PMID 41148812 3 individuals from 3 unrelated families with heterozygous NAA16 variants (p.R70C missense de novo; p.L765fs and p.E630fs frameshifts unclear inheritance) presenting with congenital heart disease (atrial septal defect, Tetralogy of Fallot, conotruncal defects). These 3 families were identified in a large cohort from the Paediatric Cardiac Genomic Consortium (PMID: 23665959, PMID: 28991257). One of the individuals with a frameshift is also listed as having a neurodevelopmental phenotype PMID: 28991257. Arg70Cys has 24 hets in gnomad and the gene is not very constrained for LOF.

PMID 41148812 Drosophila cardiac‑specific rescue assay shows loss‑of‑function for the missense variant (unable to rescue the phenotype), supporting pathogenicity.
Sources: Literature
Mendeliome v1.3554 NMNAT3 Chirag Patel Marked gene: NMNAT3 as ready
Mendeliome v1.3554 NMNAT3 Chirag Patel Gene: nmnat3 has been classified as Red List (Low Evidence).
Mendeliome v1.3554 Chirag Patel Copied gene NMNAT3 from panel Red cell disorders
Mendeliome v1.3554 NMNAT3 Chirag Patel gene: NMNAT3 was added
gene: NMNAT3 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NMNAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT3 were set to 41100733, 24739386
Phenotypes for gene: NMNAT3 were set to Familial hemolytic anemia, MONDO:0003689
Mendeliome v1.3553 CASP1 Chirag Patel Marked gene: CASP1 as ready
Mendeliome v1.3553 CASP1 Chirag Patel Gene: casp1 has been classified as Red List (Low Evidence).
Mendeliome v1.3553 Chirag Patel Copied gene CASP1 from panel Defects of intrinsic and innate immunity
Mendeliome v1.3553 CASP1 Chirag Patel gene: CASP1 was added
gene: CASP1 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP1 were set to 41101739
Phenotypes for gene: CASP1 were set to Absent IL18 and lymphopenia but no clinical disease
Mendeliome v1.3552 NOL10 Sangavi Sivagnanasundram gene: NOL10 was added
gene: NOL10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOL10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOL10 were set to 41093997
Phenotypes for gene: NOL10 were set to NOL10-related neurological disorder MONDO:0100545
Review for gene: NOL10 was set to RED
Added comment: 12yr F with recurrent focal seizures, progressive memory impairment and atrophy and parietal gliosis on MRI. Homozygous missense variant was identified (NM_024894.4: c.682 A > C; p.Asn228His). The variant is absent in gnomAD v4.1

Functional study using patient-derived fibroblasts was conducted and showed defective ribosome biogenesis. As this is a new gene disease association, it is unclear if that is the mechanism of disease. Need more evidence to promote the gene to Amber.
Sources: Literature
Mendeliome v1.3551 AP1B1 Chirag Patel Phenotypes for gene: AP1B1 were changed from Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440 to Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440
Mendeliome v1.3551 AP1B1 Chirag Patel Phenotypes for gene: AP1B1 were changed from Keratitis-ichthyosis-deafness syndrome, autosomal recessive, MIM# 242150 to Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440
Mendeliome v1.3550 AP1B1 Chirag Patel Publications for gene: AP1B1 were set to 31630791, 31630788, 33452671, 33349978, 35144013, 37657632, 32969855
Mendeliome v1.3550 AP1B1 Chirag Patel Publications for gene: AP1B1 were set to 31630788; 31630791
Mendeliome v1.3549 AP1B1 Chirag Patel reviewed gene: AP1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31630791, 31630788, 33452671, 33349978, 35144013, 37657632, 32969855; Phenotypes: Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3549 AP1S1 Chirag Patel reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19057675, 23423674, 30244301, 32306098, 24754424, 39541497; Phenotypes: MEDNIK syndrome, MONDO:0012251; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3549 ZNF334 Sarah Milton gene: ZNF334 was added
gene: ZNF334 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF334 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF334 were set to PIMD: 41168503
Phenotypes for gene: ZNF334 were set to Familial cold autoinflammatory syndrome, MONDO:0018768, ZNF334-related
Review for gene: ZNF334 was set to RED
Added comment: ZNF334 encodes zinc finger protein 334 and function is not clearly defined.

PMID: 41168503 describes 1 individual with late onset cold induced autoinflammatory disease (urticaria, fever, arthralgia, lymphadenopathy, onset 40 yo) and progressive SNHL.

Functional studies indicated reduced interaction ZNF334 and HSP90 (a cold stress regulator protein), monocytic cells lines with truncated ZNF344 showed enhanced cold induced TNF/NFKB1/NLRP3/STAT3 signalling.

This variant was truncating NMD escape, however the gene has pLI = 0.
Further literature is required.
Sources: Literature
Mendeliome v1.3548 NUDT6 Zornitza Stark Phenotypes for gene: NUDT6 were changed from Osteogenesis imperfecta to Osteogenesis imperfecta, MONDO:0019019, NUDT6-related
Mendeliome v1.3547 NUDT6 Zornitza Stark Marked gene: NUDT6 as ready
Mendeliome v1.3547 NUDT6 Zornitza Stark Gene: nudt6 has been classified as Red List (Low Evidence).
Mendeliome v1.3547 QSER1 Zornitza Stark Marked gene: QSER1 as ready
Mendeliome v1.3547 QSER1 Zornitza Stark Gene: qser1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3547 QSER1 Zornitza Stark Classified gene: QSER1 as Amber List (moderate evidence)
Mendeliome v1.3547 QSER1 Zornitza Stark Gene: qser1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3546 WRAP73 Zornitza Stark Phenotypes for gene: WRAP73 were changed from Microsperophakia to Anterior segment dysgenesis, MONDO:0019503, WRAP73-related
Mendeliome v1.3545 WRAP73 Rylee Peters reviewed gene: WRAP73: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Anterior segment dysgenesis, MONDO:0019503, WRAP73-related; Mode of inheritance: None
Mendeliome v1.3545 QSER1 Sarah Milton gene: QSER1 was added
gene: QSER1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: QSER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: QSER1 were set to PMID: 41139957
Phenotypes for gene: QSER1 were set to Neurodevelopmental disorder, MONDO:0700092, QSER1-related
Review for gene: QSER1 was set to AMBER
Added comment: QSER1 encodes glutamine and serine rich protein 1 of which the function is not clearly defined however is thought to have a role in methylation.

PMID: 41139957 describes 3 individuals with de novo heterozygous variants in QSER1 without clear consistent phenotypes.
2 individuals were born at less than 26 weeks with developmental delay with the individual that was born at term found to have normal development. Other associated features noted were ophthalmologic abnormalities (2), genitourinary abnormalities (2), congenital cardiac abnormalities (2), hemiparesis/gait abnormalities (1), preaxial polydactyly (1).

Variant types included frameshift and splice site.
One variant was present in 3 hets in gnomAD v4 with the others absent.

Functional studies demonstrated widespread expression of the protein in zebrafish without further experiments to examine molecular mechanism of variants or downstream effects.
Sources: Literature
Mendeliome v1.3544 SOX3 Chirag Patel Classified gene: SOX3 as Green List (high evidence)
Mendeliome v1.3544 SOX3 Chirag Patel Gene: sox3 has been classified as Green List (High Evidence).
Mendeliome v1.3543 Chirag Patel Added reviews for gene SOX3 from panel Pituitary hormone deficiency
Mendeliome v1.3542 CCNK Sangavi Sivagnanasundram Marked gene: CCNK as ready
Mendeliome v1.3542 CCNK Sangavi Sivagnanasundram Gene: ccnk has been classified as Green List (High Evidence).
Mendeliome v1.3542 CCNK Sangavi Sivagnanasundram Classified gene: CCNK as Green List (high evidence)
Mendeliome v1.3542 CCNK Sangavi Sivagnanasundram Gene: ccnk has been classified as Green List (High Evidence).
Mendeliome v1.3541 CCNK Sangavi Sivagnanasundram changed review comment from: CCNK encodes a regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases.
Reported affected individuals presented with a syndromic neurodevelopmental disorder (i.e. DD, ID, language impairment and various dysmorphic features)
7 unrelated families with different de novo variants (missense and CNV, deletion). All variants were either rare for AD gene or absent in gnomAD v4.1.
Supportive functional studies (knockdown zebrafish and mouse model) showed recapitulation of human phenotype and was supportive of LoF as the mechanism of disease
Sources: Literature; to: CCNK encodes a regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases.
Reported affected individuals presented with a syndromic neurodevelopmental disorder (i.e. DD, ID, language impairment and various dysmorphic features)
7 unrelated families with different de novo variants (missense and CNV, deletion). All variants were absent in gnomAD v4.1.
Supportive functional studies (knockdown zebrafish and mouse model) showed recapitulation of human phenotype and was supportive of LoF as the mechanism of disease
Sources: Literature
Mendeliome v1.3541 CCNK Sangavi Sivagnanasundram gene: CCNK was added
gene: CCNK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCNK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCNK were set to 41101726; 37597256; 30122539
Phenotypes for gene: CCNK were set to CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome MONDO:0035775
Review for gene: CCNK was set to GREEN
Added comment: CCNK encodes a regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases.
Reported affected individuals presented with a syndromic neurodevelopmental disorder (i.e. DD, ID, language impairment and various dysmorphic features)
7 unrelated families with different de novo variants (missense and CNV, deletion). All variants were either rare for AD gene or absent in gnomAD v4.1.
Supportive functional studies (knockdown zebrafish and mouse model) showed recapitulation of human phenotype and was supportive of LoF as the mechanism of disease
Sources: Literature
Mendeliome v1.3540 FOXA2 Chirag Patel Phenotypes for gene: FOXA2 were changed from Hyperinsulinism MONDO:0002177 to Hyperinsulinism MONDO:0002177; Hypopituitarism, MONDO:0005152
Publications for gene FOXA2 were changed from 29329447; 28973288; 11445544; 33999151; 30414530; 33729509; 31294511 to 29329447; 28973288; 11445544; 33999151; 30414530; 33729509; 31294511
Mendeliome v1.3539 Chirag Patel Added reviews for gene FOXA2 from panel Pituitary hormone deficiency
Mendeliome v1.3538 Chirag Patel Copied gene NUDT6 from panel Osteogenesis Imperfecta and Osteoporosis
Mendeliome v1.3538 NUDT6 Chirag Patel gene: NUDT6 was added
gene: NUDT6 was added to Mendeliome. Sources: Expert List
Mode of inheritance for gene: NUDT6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUDT6 were set to Osteogenesis imperfecta
Mendeliome v1.3537 TAPT1 Chirag Patel Classified gene: TAPT1 as Green List (high evidence)
Mendeliome v1.3537 TAPT1 Chirag Patel Gene: tapt1 has been classified as Green List (High Evidence).
Mendeliome v1.3536 Chirag Patel Added reviews for gene TAPT1 from panel Osteogenesis Imperfecta and Osteoporosis
Mendeliome v1.3535 SRRM1 Zornitza Stark Marked gene: SRRM1 as ready
Mendeliome v1.3535 SRRM1 Zornitza Stark Gene: srrm1 has been classified as Green List (High Evidence).
Mendeliome v1.3535 Zornitza Stark Copied gene SRRM1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3535 SRRM1 Zornitza Stark gene: SRRM1 was added
gene: SRRM1 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SRRM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM1 were set to 41145827
Phenotypes for gene: SRRM1 were set to Neurodevelopmental disorder, MONDO:0700092, SRRM1-related
Mendeliome v1.3534 ZNF81 Rylee Peters Tag disputed tag was added to gene: ZNF81.
Mendeliome v1.3534 SGSM3 Zornitza Stark Phenotypes for gene: SGSM3 were changed from Neurodevelopmental disorder (MONDO:0700092), SGSM3-related to Intellectual developmental disorder, autosomal recessive 84, MIM# 620401
Mendeliome v1.3533 SGSM3 Zornitza Stark reviewed gene: SGSM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 84, MIM# 620401; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3533 EPB41 Bryony Thompson Mode of inheritance for gene: EPB41 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3532 KHDC3L Bryony Thompson Added comment: Comment on mode of inheritance: No evidence of monoallelic association in the literature
Mendeliome v1.3532 KHDC3L Bryony Thompson Mode of inheritance for gene: KHDC3L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3531 EIF4A2 Bryony Thompson Mode of inheritance for gene: EIF4A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3530 EGR2 Bryony Thompson Mode of inheritance for gene: EGR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3529 PHGDH Sangavi Sivagnanasundram reviewed gene: PHGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005786; Phenotypes: Neurometabolic disorder due to serine deficiency MONDO:0018162; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3529 RHOA Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy to Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic, MIM# 618727
Mendeliome v1.3528 RHOA Zornitza Stark Publications for gene: RHOA were set to 31570889; 31821646
Mendeliome v1.3527 RHOA Zornitza Stark edited their review of gene: RHOA: Changed phenotypes: Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic, MIM# 618727
Mendeliome v1.3527 RHOA Zornitza Stark edited their review of gene: RHOA: Added comment: PMID 40414526: non-mosaic individual reported.; Changed publications: 31821646, 40414526
Mendeliome v1.3527 CARS Zornitza Stark Tag new gene name tag was added to gene: CARS.
Mendeliome v1.3527 CARS Zornitza Stark Phenotypes for gene: CARS were changed from Intellectual disability; microcephaly; brittle hair and nails to Microcephaly, developmental delay, and brittle hair syndrome, MIM# 618891
Mendeliome v1.3526 CARS Zornitza Stark Publications for gene: CARS were set to PMID: 30824121
Mendeliome v1.3525 CARS Zornitza Stark reviewed gene: CARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 41121266, 39963003, 30824121; Phenotypes: Microcephaly, developmental delay, and brittle hair syndrome, MIM# 618891; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3525 PAN2 Zornitza Stark Phenotypes for gene: PAN2 were changed from Syndromic disease MONDO:0002254, PAN2-related to Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Mendeliome v1.3524 PAN2 Zornitza Stark edited their review of gene: PAN2: Changed phenotypes: Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Mendeliome v1.3524 IL27RA Zornitza Stark Phenotypes for gene: IL27RA were changed from Epstein-Barr virus infection MONDO:0005111 , IL27RA-related to Immunodeficiency 134 (Epstein-Barr virus-specific), MIM# 621405
Mendeliome v1.3523 IL27RA Zornitza Stark reviewed gene: IL27RA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 134 (Epstein-Barr virus-specific), MIM# 621405; Mode of inheritance: None
Mendeliome v1.3523 RRP12 Zornitza Stark Marked gene: RRP12 as ready
Mendeliome v1.3523 RRP12 Zornitza Stark Gene: rrp12 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3523 RRP12 Zornitza Stark Phenotypes for gene: RRP12 were changed from Brain calcifications to Syndromic disease, MONDO:0002254, RRP12-related; Brain calcifications
Mendeliome v1.3522 RRP12 Zornitza Stark Mode of pathogenicity for gene: RRP12 was changed from Other to None
Mendeliome v1.3521 RRP12 Zornitza Stark Classified gene: RRP12 as Amber List (moderate evidence)
Mendeliome v1.3521 RRP12 Zornitza Stark Gene: rrp12 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3520 RRP12 Catherine Dalzell gene: RRP12 was added
gene: RRP12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RRP12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRP12 were set to PMID: 41059649
Phenotypes for gene: RRP12 were set to Brain calcifications
Penetrance for gene: RRP12 were set to unknown
Mode of pathogenicity for gene: RRP12 was set to Other
Review for gene: RRP12 was set to AMBER
Added comment: Variants: 5 individuals from 3 unrelated families with homozygous RRP12 variants (3 different variants, 2 consanguineous families with same variant, 2 siblings with same variant).

Phenotype: all individuals had brain calcifications (varying distribution, severity and age of onset). The patients from the two consanguineous families both had infantile-onset generalised dystonia, spasticity and severe speech impairment with widespread brain calcifications. One also had microcephaly, seizures and a cataract whilst the other had mild thrombocytopenia. The two siblings had psychiatric symptoms (one bipolar disease and one anxiety) with marked, bilateral symmetric calcifications. One also had cerebellar ataxia, choreic movements, cognitive impairment and subtle Parkinsonism whilst the other had chronic tinnitus. The final individual had dizziness and only faint bilateral lenticular calcifications.

Functional data: a statistically significant reduction in RRP12 protein levels in probands’ fibroblasts compared to controls was demonstrated. rrp12 knockdown in zebrafish embryos demonstrated reduced survival (50% survival at 2 days and maximum survival of 6 days compared to 100% survival at 6 days in controls). Phenotype abnormalities (delayed development and crimping) were also seen in the rrp12 knockdown embryos. Functional studies support a possible LoF mechanism.
Sources: Literature
Mendeliome v1.3520 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from Mental retardation, autosomal recessive 40, MIM# 615599 to Intellectual development disorder, autosomal recessive 40, MIM# 615599
Mendeliome v1.3519 TAF2 Zornitza Stark edited their review of gene: TAF2: Changed phenotypes: Intellectual development disorder, autosomal recessive 40, MIM# 615599
Mendeliome v1.3519 OSBPL2 Zornitza Stark Publications for gene: OSBPL2 were set to 25077649; 25759012; 31451425; 30894143
Mendeliome v1.3518 OSBPL2 Zornitza Stark reviewed gene: OSBPL2: Rating: RED; Mode of pathogenicity: None; Publications: 38701954; Phenotypes: Dyschromatosis, ichthyosis, deafness, and atopic disease, MIM# 621400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3518 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from Galactosialidosis, MIM# 256540; Cathepsin A-related arteriopathy with strokes and leukoencephalopathy to Galactosialidosis, MIM# 256540; Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394
Mendeliome v1.3517 CTSA Zornitza Stark edited their review of gene: CTSA: Changed phenotypes: Galactosialidosis, MIM# 256540, Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394
Mendeliome v1.3517 EPO Zornitza Stark Phenotypes for gene: EPO were changed from erythrocytosis, familial, 5 MONDO:0033483 to Erythrocytosis, familial, 5, MIM# 617907; Diamond-Blackfan anaemia-like, MIM# 617911
Mendeliome v1.3516 EPO Zornitza Stark Publications for gene: EPO were set to 27651169; 29514032; 25985138; 28283061
Mendeliome v1.3515 EPO Zornitza Stark Mode of pathogenicity for gene: EPO was changed from Other to None
Mendeliome v1.3514 EPO Zornitza Stark Mode of inheritance for gene: EPO was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3513 EPO Zornitza Stark reviewed gene: EPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 27651169, 29514032, 32130275, 20700488, 30507031, 28283061, 41137542; Phenotypes: Erythrocytosis, familial, 5, MIM# 617907, Diamond-Blackfan anaemia-like, MIM# 617911; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3513 IRF3 Bryony Thompson Publications for gene: IRF3 were set to 26513235
Mendeliome v1.3512 IRF3 Bryony Thompson reviewed gene: IRF3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32972995, 38665565, 33386334, 41065760, 26216125, 26513235; Phenotypes: Inborn error of immunity MONDO:0003778; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3512 IFNGR2 Zornitza Stark Deleted their comment
Mendeliome v1.3512 IFNGR2 Zornitza Stark edited their review of gene: IFNGR2: Added comment: PMID 23161749: some evidence that haploinsufficiency causes mono-allelic disease. Amber for this association.; Changed publications: 15924140, 18625743, 31222290, 23161749, 23161749; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3512 NLRP12 Zornitza Stark reviewed gene: NLRP12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3512 CXorf56 Zornitza Stark Marked gene: CXorf56 as ready
Mendeliome v1.3512 CXorf56 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is STEEP1
Mendeliome v1.3512 CXorf56 Zornitza Stark Gene: cxorf56 has been classified as Green List (High Evidence).
Mendeliome v1.3512 CXorf56 Zornitza Stark Publications for gene: CXorf56 were set to 29374277
Mendeliome v1.3511 CXorf56 Zornitza Stark Phenotypes for gene: CXorf56 were changed from Mental retardation, X-linked 107, MIM# 301013 to Intellectual developmental disorder, X-linked 107, MIM# 301013
Mendeliome v1.3510 CXorf56 Zornitza Stark Tag new gene name tag was added to gene: CXorf56.
Mendeliome v1.3510 SKOR2 Zornitza Stark Phenotypes for gene: SKOR2 were changed from complex neurodevelopmental disorder with motor features MONDO:0100516 to Valence-Farazi cerebellar ataxia syndrome, MIM# 621386
Mendeliome v1.3509 SKOR2 Zornitza Stark reviewed gene: SKOR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Valence-Farazi cerebellar ataxia syndrome, MIM# 621386; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3509 TBX19 Chirag Patel Source Victorian Clinical Genetics Services was removed from TBX19.
Source Expert List was added to TBX19.
Publications for gene TBX19 were changed from 15613420, 31998673, 11290323, 15476446, 22170728 to 15613420, 31998673, 11290323, 15476446, 22170728
Mendeliome v1.3508 LCP1 Zornitza Stark Phenotypes for gene: LCP1 were changed from Bone marrow failure syndrome, MONDO:0000159, LCP1-related to Combined immunodeficiency, MONDO:0015131, LCP1-related
Mendeliome v1.3507 LCP1 Zornitza Stark Publications for gene: LCP1 were set to 38710235
Mendeliome v1.3506 LCP1 Zornitza Stark Classified gene: LCP1 as Green List (high evidence)
Mendeliome v1.3506 LCP1 Zornitza Stark Gene: lcp1 has been classified as Green List (High Evidence).
Mendeliome v1.3505 LCP1 Sarah Milton changed review comment from: LCP1 encodes lymphocyte cytosolic protein and has a role in actin cross-linking in haematopoietic cells.

PMID: 41056520 describes 4 families with 10 affected individuals who presented with neutropenia +/- lymphopenia and hypogammaglobulinemia. 2 individuals developed acute leukemia.

Variant type included missense, splice and inframe del. Appears there is some genotype phenotype correlation in regards to severity of disease.
All variants appropriately rare in gnomAD v4.

Supportive functional studies with IPSC produced with variant seen in affected individuals, these haematopoietic progenitors failed to produce CFU-G colonies with rescue upon introduction of gene corrected cells.

PMID: 41056520 describes additional family with 5 affected individuals who also had neutropenia +/- lymphopenia, hypogammaglobulinemia as well as deafness.; to: LCP1 encodes lymphocyte cytosolic protein and has a role in actin cross-linking in haematopoietic cells.

PMID: 41056520 describes 4 families with 10 affected individuals who presented with neutropenia +/- lymphopenia and hypogammaglobulinemia. 2 individuals developed acute leukemia.

Variant type included missense, splice and inframe del. Appears there is some genotype phenotype correlation in regards to severity of disease.
All variants appropriately rare in gnomAD v4.

Supportive functional studies with IPSC produced with variant seen in affected individuals, these haematopoietic progenitors failed to produce CFU-G colonies with rescue upon introduction of gene corrected cells.
Exact mechanism of disease remains unclear.

PMID: 41056520 describes additional family with 5 affected individuals who also had neutropenia +/- lymphopenia, hypogammaglobulinemia as well as deafness.
Mendeliome v1.3505 LCP1 Sarah Milton reviewed gene: LCP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40510848, PMID: 41056520; Phenotypes: Combined immunodeficiency, MONDO:0015131, LCP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3505 SLC27A3 Zornitza Stark Marked gene: SLC27A3 as ready
Mendeliome v1.3505 SLC27A3 Zornitza Stark Gene: slc27a3 has been classified as Red List (Low Evidence).
Mendeliome v1.3505 YTHDC2 Zornitza Stark Marked gene: YTHDC2 as ready
Mendeliome v1.3505 YTHDC2 Zornitza Stark Gene: ythdc2 has been classified as Green List (High Evidence).
Mendeliome v1.3505 Zornitza Stark Copied gene YTHDC2 from panel Primary Ovarian Insufficiency_Premature Ovarian Failure
Mendeliome v1.3505 YTHDC2 Zornitza Stark gene: YTHDC2 was added
gene: YTHDC2 was added to Mendeliome. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: YTHDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YTHDC2 were set to 29033321, 29360036, 35138268
Phenotypes for gene: YTHDC2 were set to Primary ovarian failure, MONDO:0005387
Mendeliome v1.3504 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903
Mendeliome v1.3503 OTUD7A Zornitza Stark Classified gene: OTUD7A as Green List (high evidence)
Mendeliome v1.3503 OTUD7A Zornitza Stark Gene: otud7a has been classified as Green List (High Evidence).
Mendeliome v1.3502 OTUD7A Zornitza Stark Tag SV/CNV tag was added to gene: OTUD7A.
Mendeliome v1.3502 ARMC5 Zornitza Stark Marked gene: ARMC5 as ready
Mendeliome v1.3502 ARMC5 Zornitza Stark Gene: armc5 has been classified as Green List (High Evidence).
Mendeliome v1.3502 PPIB Zornitza Stark Publications for gene: PPIB were set to 19781681; 32392875
Mendeliome v1.3501 PPIB Zornitza Stark Mode of inheritance for gene: PPIB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3500 PPIB Zornitza Stark edited their review of gene: PPIB: Changed publications: 19781681, 32392875, 41045073; Changed phenotypes: Osteogenesis imperfecta, type IX, MIM# 259440, Optic atrophy (MONDO:0003608), PPIB-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3500 SLC27A3 Sarah Milton gene: SLC27A3 was added
gene: SLC27A3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC27A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC27A3 were set to PMID: 41054338
Phenotypes for gene: SLC27A3 were set to Inherited neurodegenerative disorder, MONDO:0024237, SLC27A3-related
Review for gene: SLC27A3 was set to RED
Added comment: SLC27A3 encodes for very long chain acyl CoA synthetase 3 which function to catalyse the formation of fatty acyl coA using long and very long chain fatty acids as substrates.

PMID: 41054338 describes one individual with a presumed homozgous stop gain variant in SLC27A3 who presented with progressive ataxia, optic atrophy, cognitive deterioration, mood disorder and progressive cortical atrophy on MRI-B.
Onset of symptoms at 18 months with significant progression from 12 years of age.
Duo exome testing performed (not segregated in both parents).

No homozygous LOF variants in gnomAD v4.

Some supportive functional data in paper with no protein expressed in patient cells as detected by western blot and patient's cells were found to have more neutral lipids than controls.

More literature is required to increase the robustness of this assertion.
Sources: Literature
Mendeliome v1.3499 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Mendeliome v1.3499 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Mendeliome v1.3498 TMEM17 Chirag Patel Phenotypes for gene: TMEM17 were changed from Meckel syndrome MONDO:0018921; TMEM17-related to Meckel syndrome MONDO:0018921, TMEM17-related
Mendeliome v1.3497 TMEM17 Chirag Patel Publications for gene TMEM17 were changed from 41054827, 40841990 to 41054827, 40841990
Mendeliome v1.3496 FCN3 Zornitza Stark Classified gene: FCN3 as Red List (low evidence)
Mendeliome v1.3496 FCN3 Zornitza Stark Gene: fcn3 has been classified as Red List (Low Evidence).
Mendeliome v1.3496 TMEM17 Chirag Patel Classified gene: TMEM17 as Green List (high evidence)
Mendeliome v1.3496 TMEM17 Chirag Patel Gene: tmem17 has been classified as Green List (High Evidence).
Mendeliome v1.3495 FCN3 Zornitza Stark edited their review of gene: FCN3: Added comment: Same recurrent hmz variant in all reported cases, downgrade.; Changed rating: RED
Mendeliome v1.3495 OTUD7A Rylee Peters reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29395075, 31997314, 33381903, 36180924, 41028987; Phenotypes: Neurodevelopmental disorder with hypotonia and seizures (MIM#620790), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3495 TMEM17 Chirag Patel edited their review of gene: TMEM17: Added comment: 2 additional unrelated fetuses with clinical diagnosis of Meckel-Gruber syndrome (occipital encephalocele, polydactyly, and kidney cysts). WES identified a founder homozygous missense variant (Arg94Trp) in TMEM17 gene.

Comprehensive functional analyses of all known TMEM17 variants, using patient tissues/cells and a C. elegans model system, demonstrate a loss-of-function mechanism. The study reveals severe functional consequences, including TMEM17 destabilization and mislocalization, anomalies in cilium composition and function, and abrogation of Sonic Hedgehog signaling.; Changed rating: GREEN; Changed publications: 41054827, 40841990
Mendeliome v1.3495 PRKACA Chirag Patel Source Literature was removed from PRKACA.
Source Expert Review was added to PRKACA.
Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability; Pigmented nodular adrenocortical disease, primary, 4, MONDO:0014359
Publications for gene PRKACA were changed from 33058759; 31130284; 24571724, 25924874, 40066253, 37988664, 39006359 to 33058759; 31130284; 24571724, 25924874, 40066253, 37988664, 39006359
Mendeliome v1.3494 PDE11A Chirag Patel Source Victorian Clinical Genetics Services was removed from PDE11A.
Source Expert List was added to PDE11A.
Phenotypes for gene: PDE11A were changed from Pigmented nodular adrenocortical disease, primary, 2 - MIM#610475 to Pigmented nodular adrenocortical disease, primary, 2, MONDO:0012505
Publications for gene PDE11A were changed from 16767104; 18559625; 21047926; 17178847; 39006359, 20351491, 18491255, 18559625 to 16767104; 18559625; 21047926; 17178847; 39006359, 20351491, 18491255, 18559625
Mendeliome v1.3493 PDE8B Chirag Patel Source Victorian Clinical Genetics Services was removed from PDE8B.
Phenotypes for gene: PDE8B were changed from Striatal degeneration, autosomal dominant, MIM#609161 to Striatal degeneration, autosomal dominant, MIM#609161; Pigmented nodular adrenocortical disease, primary, 3, MONDO:0013616
Publications for gene PDE8B were changed from 20085714; 26769607; 26475694; 39006359, 32097969, 18272904, 25971952, 22335482, 18431404 to 20085714; 26769607; 26475694; 39006359, 32097969, 18272904, 25971952, 22335482, 18431404
Mendeliome v1.3492 Chirag Patel Copied gene ARMC5 from panel Primary pigmented nodular adrenocortical disease
Mendeliome v1.3492 ARMC5 Chirag Patel gene: ARMC5 was added
gene: ARMC5 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ARMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARMC5 were set to 39910635, 41042544, 25853793, 24283224, 24601692, 24708098, 24905064, 39006359, 32097969
Phenotypes for gene: ARMC5 were set to ACTH-independent macronodular adrenal hyperplasia 2, MONDO:0014416
Mendeliome v1.3491 PPIB Rylee Peters reviewed gene: PPIB: Rating: GREEN; Mode of pathogenicity: None; Publications: 41045073; Phenotypes: Osteogenesis imperfecta, type IX, MIM# 259440, Optic atrophy (MONDO:0003608), PPIB-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3491 PRKACA Chirag Patel reviewed gene: PRKACA: Rating: GREEN; Mode of pathogenicity: Other; Publications: 24571724, 25924874, 40066253, 37988664, 39006359; Phenotypes: Pigmented nodular adrenocortical disease, primary, 4, MONDO:0014359; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3491 PDE8B Chirag Patel reviewed gene: PDE8B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39006359, 32097969, 18272904, 25971952, 22335482, 18431404; Phenotypes: Pigmented nodular adrenocortical disease, primary, 3, MONDO:0013616; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3491 PDE11A Chirag Patel Classified gene: PDE11A as Green List (high evidence)
Mendeliome v1.3491 PDE11A Chirag Patel Gene: pde11a has been classified as Green List (High Evidence).
Mendeliome v1.3490 PDE11A Chirag Patel reviewed gene: PDE11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39006359, 16767104, 20351491, 18491255, 18559625; Phenotypes: Pigmented nodular adrenocortical disease, primary, 2, MONDO:0012505; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3490 SLC31A1 Rylee Peters reviewed gene: SLC31A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41040850; Phenotypes: Neurodegeneration and seizures due to copper transport defect MIM#620306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3490 DIP2B_FRA12A_CGG Bryony Thompson Publications for STR: DIP2B_FRA12A_CGG were set to 17236128
Mendeliome v1.3489 DIP2B_FRA12A_CGG Bryony Thompson edited their review of STR: DIP2B_FRA12A_CGG: Added comment: Unsure about the expansions association with disease due to variable phenotypes and possible incomplete penetrance PMID 17236128, 39854091, and 41028987 report 23 unrelated families with heterozygous CGG repeat expansions in the 5′UTR of DIP2B. Sixteen families present with intellectual disability associated with the FRA12A fragile site, while seven families (including two siblings, five ataxia probands, and one dystonia case) exhibit neurodevelopmental disability with progressive movement disorders (chorea, dystonia, ataxia). Functional studies demonstrate reduced DIP2B expression via promoter hypermethylation. Segregation analysis shows segregation from unaffected parents (possibly reduced penetrance) and de novo events. DIP2B expansion OR 2.8 (p=0.04) in ataxia cohort (5/788) vs gnomAD.; Changed publications: 17236128, 33510257, 39854091, 41028987; Changed phenotypes: intellectual disability, FRA12A type MONDO:0007634
Mendeliome v1.3489 CFAP74 Zornitza Stark Phenotypes for gene: CFAP74 were changed from Primary ciliary dyskinesia; infertility to ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353
Mendeliome v1.3488 CFAP74 Zornitza Stark Classified gene: CFAP74 as Green List (high evidence)
Mendeliome v1.3488 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Green List (High Evidence).
Mendeliome v1.3487 RBM15 Zornitza Stark Marked gene: RBM15 as ready
Mendeliome v1.3487 RBM15 Zornitza Stark Gene: rbm15 has been classified as Red List (Low Evidence).
Mendeliome v1.3487 SSPO Zornitza Stark Marked gene: SSPO as ready
Mendeliome v1.3487 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Mendeliome v1.3487 SSPO Zornitza Stark Classified gene: SSPO as Green List (high evidence)
Mendeliome v1.3487 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Mendeliome v1.3486 PPFIA2 May Tun Hla Maw changed review comment from: Encodes Liprin-alpha2.
Predominantly expressed in brain in the pre- and post-synaptic compartments.
Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains.

Gene-disease association: neurodevelopmental disorder.
Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism.

Evidence summary:
Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD.

Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia.

Functional studies:
Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype.
Sources: Literature; to: Encodes Liprin-alpha2.
Predominantly expressed in brain in the pre- and post-synaptic compartments.
Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains.

Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism.

Evidence summary:
Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD.

Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia.

Functional studies:
Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype.
Sources: Literature
Mendeliome v1.3486 SSPO Sarah Milton changed review comment from: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature; to: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which is a large secreted glycoprotein that plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature
Mendeliome v1.3486 SSPO Sarah Milton gene: SSPO was added
gene: SSPO was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: SSPO.
Mode of inheritance for gene: SSPO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SSPO were set to PMID: 41077560
Phenotypes for gene: SSPO were set to Neurodevelopmental disorder, MONDO:0700092, SSPOP-related
Review for gene: SSPO was set to GREEN
Added comment: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature
Mendeliome v1.3485 RBM15 Sangavi Sivagnanasundram gene: RBM15 was added
gene: RBM15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBM15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBM15 were set to 41058181
Phenotypes for gene: RBM15 were set to Congenital mirror movements, RBM15-related, MONDO:0016558
Review for gene: RBM15 was set to RED
Added comment: One 27-year-old proband reported with mild mirror movements affecting only hands.
De novo heterozygous was identified in the affected individual and absent from asymptomatic parents - p.Ser175Lysfs∗8 - absent in gnomADv4.1
RBM15 is constraint for LOF according to gnomAD v4.1 [pLI = 1;o/e = 0.11 (0.06 - 0.21)] however, LoF isn't an established mechanism of disease.
Sources: Literature
Mendeliome v1.3484 CFAP74 Sangavi Sivagnanasundram changed review comment from: Additional reported individuals supporting gene-disease association.; to: Additional reported individuals in four unrelated families supporting gene-disease association.
Mendeliome v1.3484 CFAP74 Sangavi Sivagnanasundram reviewed gene: CFAP74: Rating: GREEN; Mode of pathogenicity: None; Publications: 41078601, 39362668, 36459505, 32555313; Phenotypes: ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3484 SNAI2 Sangavi Sivagnanasundram reviewed gene: SNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 41073431; Phenotypes: Waardenburg syndrome type 2D MONDO:0012144; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3484 PPFIA2 Zornitza Stark Marked gene: PPFIA2 as ready
Mendeliome v1.3484 PPFIA2 Zornitza Stark Gene: ppfia2 has been classified as Green List (High Evidence).
Mendeliome v1.3484 PPFIA2 Zornitza Stark Mode of pathogenicity for gene: PPFIA2 was changed from Other to None
Mendeliome v1.3483 PPFIA2 Zornitza Stark Classified gene: PPFIA2 as Green List (high evidence)
Mendeliome v1.3483 PPFIA2 Zornitza Stark Gene: ppfia2 has been classified as Green List (High Evidence).
Mendeliome v1.3482 EIPR1 Zornitza Stark Marked gene: EIPR1 as ready
Mendeliome v1.3482 EIPR1 Zornitza Stark Gene: eipr1 has been classified as Green List (High Evidence).
Mendeliome v1.3482 EIPR1 Zornitza Stark Classified gene: EIPR1 as Green List (high evidence)
Mendeliome v1.3482 EIPR1 Zornitza Stark Gene: eipr1 has been classified as Green List (High Evidence).
Mendeliome v1.3481 ARHGAP19 Zornitza Stark Marked gene: ARHGAP19 as ready
Mendeliome v1.3481 ARHGAP19 Zornitza Stark Gene: arhgap19 has been classified as Green List (High Evidence).
Mendeliome v1.3481 ARHGAP19 Zornitza Stark Classified gene: ARHGAP19 as Green List (high evidence)
Mendeliome v1.3481 ARHGAP19 Zornitza Stark Gene: arhgap19 has been classified as Green List (High Evidence).
Mendeliome v1.3480 AGBL3 Bryony Thompson Marked gene: AGBL3 as ready
Mendeliome v1.3480 AGBL3 Bryony Thompson Gene: agbl3 has been classified as Red List (Low Evidence).
Mendeliome v1.3480 AGBL3 Bryony Thompson gene: AGBL3 was added
gene: AGBL3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AGBL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGBL3 were set to 41042736
Phenotypes for gene: AGBL3 were set to Hypocomplementemic urticarial vasculitis MONDO:0018227
Review for gene: AGBL3 was set to RED
Added comment: PMID:41042736 reports one patient from a single consanguineous family with biallelic loss‑of‑function AGBL3 variant presenting with hypocomplementemic urticarial vasculitis syndrome, childhood‑onset fever, urticarial rash, arthralgia, and low complement levels.
Sources: Literature
Mendeliome v1.3479 EIPR1 Thomas Cloney gene: EIPR1 was added
gene: EIPR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIPR1 were set to 41058046
Phenotypes for gene: EIPR1 were set to Mendelian neurodevelopmental disorder MONDO:0100500, EIPR1-related
Penetrance for gene: EIPR1 were set to unknown
Review for gene: EIPR1 was set to GREEN
Added comment: Report of 8 individuals from 6 unrelated consanguinous families with homozygous EIPR1 variants (5 different variants).
Phenotype: All had global developmental delay (range of severity), with significant motor delay (5/8 never attained walking). Neurological manifestations: 2/8 Hypotonia, 4/8 had spasticity. 5/8 had microcepahly. MRI Brain abnormalities included: delayed myelination, hypoplasia of the corpus callosum, mild cerebellar atrophy, dysmorphic lateral ventricles. (Limited phenotypic information in pre-print - all in supplementary data)
Functional data: In vitro functional work show reduced protrien levels and interaction with EARP and GARP; and in vivo zebrafish models with knowckout of EIPR1 result in neurodevelopmental and locomotor defects
Sources: Literature
Mendeliome v1.3479 PPFIA2 May Tun Hla Maw gene: PPFIA2 was added
gene: PPFIA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPFIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA2 were set to 41044885
Phenotypes for gene: PPFIA2 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA2 related
Mode of pathogenicity for gene: PPFIA2 was set to Other
Review for gene: PPFIA2 was set to GREEN
Added comment: Encodes Liprin-alpha2.
Predominantly expressed in brain in the pre- and post-synaptic compartments.
Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains.

Gene-disease association: neurodevelopmental disorder.
Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism.

Evidence summary:
Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD.

Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia.

Functional studies:
Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype.
Sources: Literature
Mendeliome v1.3479 BRSK1 Zornitza Stark Phenotypes for gene: BRSK1 were changed from Epilepsy, MONDO:0005027, BRSK1-related to Neurodevelopmental disorder, MONDO:0700092, BRSK1-related
Mendeliome v1.3478 BRSK1 Zornitza Stark Marked gene: BRSK1 as ready
Mendeliome v1.3478 BRSK1 Zornitza Stark Gene: brsk1 has been classified as Green List (High Evidence).
Mendeliome v1.3478 BRSK1 Zornitza Stark Classified gene: BRSK1 as Green List (high evidence)
Mendeliome v1.3478 BRSK1 Zornitza Stark Gene: brsk1 has been classified as Green List (High Evidence).
Mendeliome v1.3477 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 31752325; 30244537; 28594066; 28645153; 33199448; 33199448
Mendeliome v1.3476 PNPT1 Zornitza Stark edited their review of gene: PNPT1: Added comment: Additional reports for association between mono allelic variants and SCA:

PMID:39729134 (2024) reported an 11-year-old male of Indian descent with childhood-onset ataxia and severe sensorineural hearing loss. Genetic analysis identified heterozygous 3' splice site variant in the PNPT1 gene (c.2014-3 C > G).

PMID:39899068 (2025) reported a 1-year-8-month-old female proband of Brazilian descent with Spinocerebellar Ataxia 25 that presented with progressive ataxia, cerebellar atrophy, and sensory neuropathy. She was identified with a novel heterozygous truncating variant in PNPT1 (c.2068del), which she inherited from her father. Although the father was previously reported as asymptomatic, he was affected with axonal and demyelinating polyneuropathy but not ataxia upon detailed examination.

PMID:39924761 (2025) reported two unrelated families, where all individuals presented with sensory ataxic neuropathy (SAN), while some individuals developed cerebellar signs. Analysis of WGS variant data through the 100,000 Genomes Project identified two different heterozygous variants in these families. Family 1 underwent a 'quad' study and the previously reported c.2014‐3C>G variant segregated in all affected family members and was absent in all unaffected family members. Sanger sequencing confirmed segregation in two other individuals. c.2014‐3C>G is the same variant that was found in the 3-generation Australian family reported by PMID:35411967, where unaffected family members harboured the variant. A novel nonsense variant (c.2143C>T/ p.Arg715Ter) was found in both affected members of Family 2.

PMID:40757543 (2024) reported an 18-year-old male presented with slowly progressive infancy-onset spasticity of the lower limbs and cerebellar ataxia, associated with painless strabismus, intellectual disability, urinary incontinence, bilateral progressive visual loss, and cognitive decline since early adolescence. The patient was identified with a heterozygous pathogenic variant c.162-1G>A in PNPT1 gene.; Changed rating: GREEN; Changed publications: 35411967, 39729134, 39899068, 39924761, 40757543
Mendeliome v1.3476 ARHGAP19 Fahaz Nazer gene: ARHGAP19 was added
gene: ARHGAP19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGAP19 were set to 41086021
Phenotypes for gene: ARHGAP19 were set to Motor Peripheral Neuropathy; MONDO:0002316; ARHGAP19 related
Review for gene: ARHGAP19 was set to GREEN
Added comment: Biallelic LOF variants in 25 individuals from 20 unrelated families
Phenotype: motor predominant neuropathy
14/23 had assymetric lower limb involvement

Biochemical GAP assays show GAP domain variants cause loss of protein function.
RNA studies show LOF alters expression of genes linked to 3 cellular pathways, compared to controls.
iPSC-derived motor neurons show reduced ARHGAP19 expression

Models: Zebrafish, drosophila loss of function models show movement deficits.

LOF variants reported in 'GAP' domain and outside this domain with no genotype-phenotype correlation noted
Sources: Literature
Mendeliome v1.3476 BRSK1 Cara Beck gene: BRSK1 was added
gene: BRSK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BRSK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRSK1 were set to 41035394
Phenotypes for gene: BRSK1 were set to Epilepsy, MONDO:0005027, BRSK1-related
Review for gene: BRSK1 was set to GREEN
Added comment: PMID:41035394
Six novel BRSK1 variants were identified in seven probands. Five cases were de novo, two inherited. One variant was recurrent.
All had epilepsy (generalised tonic clonic seizures, absence, focal, spasms), 2/7 GDD, 1/1 'mental developmental delay', 1/7 motor delay, 2/7 normal development.
Functional work, including in a mouse model, was consistent with loss of function mechanism and supports pathogenicity of 2 frameshift, 1 nonsense, 1 missense variant, with 2 missense not yet considered pathogenic.
Sources: Literature
Mendeliome v1.3476 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 9916796; 12414817; 16611712; 18798332
Mendeliome v1.3475 ATP6V1B1 Elena Savva Mode of inheritance for gene: ATP6V1B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3474 ATP6V1B1 Elena Savva reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39837581; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM#267300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3474 KLHL20 Zornitza Stark Phenotypes for gene: KLHL20 were changed from Neurodevelopmental disorder (MONDO:0700092), KLHL20-related to Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390
Mendeliome v1.3473 KLHL20 Zornitza Stark reviewed gene: KLHL20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3473 KCTD15 Zornitza Stark Marked gene: KCTD15 as ready
Mendeliome v1.3473 KCTD15 Zornitza Stark Gene: kctd15 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3473 KCTD15 Zornitza Stark Classified gene: KCTD15 as Amber List (moderate evidence)
Mendeliome v1.3473 KCTD15 Zornitza Stark Gene: kctd15 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3472 OCRL Zornitza Stark Phenotypes for gene: OCRL were changed from Dent disease 2, MIM# 300555; Lowe syndrome , MIM#309000 to Oculocerebrorenal syndrome MONDO:0010645; Dent disease 2, MIM# 300555; Lowe syndrome , MIM#309000
Mendeliome v1.3471 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder (MONDO:0700092), SNAPIN-related to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Mendeliome v1.3470 SNAPIN Zornitza Stark reviewed gene: SNAPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3470 IFNGR2 Zornitza Stark Publications for gene: IFNGR2 were set to 15924140; 18625743; 31222290
Mendeliome v1.3469 IFNGR2 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported with bi-allelic disease.
Mendeliome v1.3469 IFNGR2 Zornitza Stark edited their review of gene: IFNGR2: Added comment: PMID 23161749: single case report of heterozygous LoF variant causing disease (but ?missed second hit).; Changed publications: 15924140, 18625743, 31222290, 23161749
Mendeliome v1.3469 LOXL3 Zornitza Stark Phenotypes for gene: LOXL3 were changed from Stickler syndrome to Stickler syndrome, MONDO:0019354, LOXL3-related
Mendeliome v1.3468 LOXL3 Zornitza Stark Publications for gene: LOXL3 were set to 30362103; 25663169
Mendeliome v1.3467 LOXL3 Zornitza Stark Classified gene: LOXL3 as Green List (high evidence)
Mendeliome v1.3467 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Green List (High Evidence).
Mendeliome v1.3466 LOXL3 Zornitza Stark changed review comment from: PMID 41052910: additional family reported, three affected sibs, compound het variants segregated with disease.; to: PMID 41052910: additional family reported, three affected sibs, compound het variants segregated with disease. Zebrafish model also available.
Mendeliome v1.3466 LOXL3 Zornitza Stark edited their review of gene: LOXL3: Added comment: PMID 41052910: additional family reported, three affected sibs, compound het variants segregated with disease.; Changed rating: GREEN; Changed publications: 30362103, 25663169, 41052910; Changed phenotypes: Stickler syndrome, MONDO:0019354, LOXL3-related
Mendeliome v1.3466 CDKL1 Zornitza Stark Classified gene: CDKL1 as Red List (low evidence)
Mendeliome v1.3466 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Red List (Low Evidence).
Mendeliome v1.3465 CDKL1 Zornitza Stark Deleted their comment
Mendeliome v1.3465 CDKL1 Zornitza Stark edited their review of gene: CDKL1: Changed rating: RED
Mendeliome v1.3465 CDKL1 Zornitza Stark Classified gene: CDKL1 as Amber List (moderate evidence)
Mendeliome v1.3465 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3464 CDKL1 Zornitza Stark edited their review of gene: CDKL1: Added comment: PMID 40088891 reports two unrelated individuals with de novo heterozygous CDKL1 missense variants (p.Val115Ala, p.Arg169Cys) presenting with childhood‑onset neurodevelopmental disorder, developmental delay and seizures; Drosophila rescue assays show dominant‑negative activity of the variants. However, note that the variants are present at low frequency in gnomAD v4, p.Val115Ala: 2 individuals, p.Arg169Cys: 13 individuals. Some supportive functional data presented. Upgrade to Amber but not Green due to pop counts.; Changed rating: AMBER; Changed publications: 40088891
Mendeliome v1.3464 TEKT3 Zornitza Stark Marked gene: TEKT3 as ready
Mendeliome v1.3464 TEKT3 Zornitza Stark Gene: tekt3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3464 Zornitza Stark Copied gene TEKT3 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.3464 TEKT3 Zornitza Stark gene: TEKT3 was added
gene: TEKT3 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TEKT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEKT3 were set to 36708031
Phenotypes for gene: TEKT3 were set to Spermatogenic failure, MONDO:0004983, TEKT3-related
Mendeliome v1.3463 OCRL Sangavi Sivagnanasundram reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: None; Publications: 1321346; Phenotypes: oculocerebrorenal syndrome MONDO:0010645; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.3463 NUS1 Sangavi Sivagnanasundram reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100083; Phenotypes: progressive myoclonus epilepsy MONDO:0020074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3463 NLRP2 Zornitza Stark Phenotypes for gene: NLRP2 were changed from female infertility; early embryonic arrest to Oocyte/zygote/embryo maturation arrest 18, MONDO:0957230
Mendeliome v1.3462 NLRP2 Zornitza Stark Publications for gene: NLRP2 were set to 30877238; 19300480; 29574422; 33090377
Mendeliome v1.3461 NLRP2 Zornitza Stark Mode of inheritance for gene: NLRP2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3460 NLRP2 Zornitza Stark edited their review of gene: NLRP2: Added comment: PMIDs 29574422, 30877238, 35643636, 39887367 and 41044650 report 15 unrelated families with rare NLRP2 variants. Maternal heterozygous variants cause multilocus imprinting disturbance (MLID) presenting as Beckwith‑Wiedemann syndrome, Silver‑Russell syndrome, transient neonatal diabetes mellitus, unspecified imprinting disorder and pseudohypoparathyroidism type‑1B. Biallelic loss‑of‑function variants cause autosomal recessive primary female infertility with early embryonic arrest (embryos arresting at the 2–4‑cell stage). Functional studies show reduced NLRP2 protein in patient‑derived cells and mouse Nlrp2 knockout recapitulating the embryonic arrest phenotype. No contradictory evidence exists for the well‑supported phenotypes.; Changed publications: 29574422, 30877238, 35643636, 39887367, 41044650
Mendeliome v1.3460 NLRP2 Zornitza Stark reviewed gene: NLRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3460 MVK Zornitza Stark Phenotypes for gene: MVK were changed from Mevalonic aciduria MIM# 610377 to Mevalonic aciduria MIM#610377; Porokeratosis 3, multiple types, MIM# 175900
Mendeliome v1.3459 MVK Zornitza Stark Mode of inheritance for gene: MVK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3458 MVK Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease associations.
Mendeliome v1.3458 MVK Zornitza Stark edited their review of gene: MVK: Changed phenotypes: Mevalonic aciduria MIM#610377, Porokeratosis 3, multiple types, MIM# 175900; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3458 LBR Zornitza Stark Phenotypes for gene: LBR were changed from Greenberg skeletal dysplasia, MIM# 215140 to Greenberg skeletal dysplasia, MIM#215140; Pelger-Huet anomaly, MIM# 169400
Mendeliome v1.3457 LBR Zornitza Stark Mode of inheritance for gene: LBR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3456 LBR Zornitza Stark changed review comment from: Overlap with ATD in particular.
Sources: Expert list; to: Well established mono- and biallelic gene-disease associations.
Sources: Expert list
Mendeliome v1.3456 LBR Zornitza Stark edited their review of gene: LBR: Changed phenotypes: Greenberg skeletal dysplasia, MIM#215140, Pelger-Huet anomaly, MIM# 169400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3456 CFAP206 Zornitza Stark Phenotypes for gene: CFAP206 were changed from Multiple morphological abnormalities of the flagella to Spermatogenic failure 102, MIM# 621387
Mendeliome v1.3455 CFAP206 Zornitza Stark reviewed gene: CFAP206: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 102, MIM# 621387; Mode of inheritance: None
Mendeliome v1.3455 MOCS3 Zornitza Stark Phenotypes for gene: MOCS3 were changed from Molybdenum cofactor deficiency MONDO:0020480 to Molybdenum cofactor deficiency, type B2, MIM# 621373
Mendeliome v1.3454 MOCS3 Zornitza Stark edited their review of gene: MOCS3: Changed phenotypes: Molybdenum cofactor deficiency, type B2, MIM# 621373
Mendeliome v1.3454 NRL Zornitza Stark Phenotypes for gene: NRL were changed from Retinitis pigmentosa 27 - MIM#613750; Retinal degeneration, autosomal recessive, clumped pigment type to Retinitis pigmentosa 27 - MIM#613750; Enhanced S-cone syndrome 2, MIM# 621371
Mendeliome v1.3453 NRL Zornitza Stark reviewed gene: NRL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Enhanced S-cone syndrome 2, MIM# 621371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3453 KCTD15 Achchuthan Shanmugasundram gene: KCTD15 was added
gene: KCTD15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCTD15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCTD15 were set to 38296633
Phenotypes for gene: KCTD15 were set to frontonasal dysplasia, MONDO:0016643
Mode of pathogenicity for gene: KCTD15 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KCTD15 was set to AMBER
Added comment: PMID:38296633 (2024) reported a two-generation family affected by a distinctive phenotype comprising a lipomatous frontonasal malformation, anosmia, cutis aplasia of the scalp and/or sparse hair, and congenital heart disease. A heterozygous c.310G>C variant encoding p.(Asp104His) within the BTB domain of KCTD15 was identified in the affected father and daughter via exome sequencing and the variant segregated with the phenotype. A de novo heterozygous c.263G>A variant encoding p.(Gly88Asp) was identified via targeted DNA sequencing in a similarly affected sporadic patient.

There is some functional evidence available from structural analyses, which demonstrated that missense substitutions act through a dominant negative mechanism by disrupting the higher order structure of the KCTD15 protein complex.
Sources: Literature
Mendeliome v1.3453 RIPOR2 Arina Puzriakova edited their review of gene: RIPOR2: Added comment: PMID: 37864412 - a distinct homozygous LOF variant (c.1561C>T (p.Arg521*)) in exon 14 of the RIPOR2 gene was identified by WES in three siblings from a consanguineous Tunisian family with non-syndromic bilateral profound hearing and vestibular dysfunctions. Parents were unaffected heterozygous carriers. No other variants in hearing loss genes were found. Zebrafish model with a stop codon inserted within ripor2 exon 14 showed that F2 larva did not exhibit a different hearing or balance behaviour compared to wild-type.; Changed publications: 24958875, 32631815, 37864412; Changed phenotypes: Deafness, autosomal dominant 21, OMIM:607017, Deafness, autosomal recessive 104, OMIM:616515; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3453 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461 to Encephalopathy, acute, infection-induced, susceptibility to, 12 MIM#620461
Mendeliome v1.3452 EXT2 Zornitza Stark Phenotypes for gene: EXT2 were changed from Seizures, scoliosis, and macrocephaly syndrome, MIM#616682 to Exostoses, multiple, type 2 MIM#133701; Seizures, scoliosis, and macrocephaly syndrome, MIM#616682
Mendeliome v1.3451 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700 to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Mendeliome v1.3450 NLRC4 Zornitza Stark Phenotypes for gene: NLRC4 were changed from Familial cold autoinflammatory syndrome 4 - MIM#616115; Autoinflammation with infantile enterocolitis - MIM#616050 to periodic fever-infantile enterocolitis-autoinflammatory syndrome MONDO:0014472
Mendeliome v1.3449 NMNAT1 Zornitza Stark Phenotypes for gene: NMNAT1 were changed from Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260; Leber congenital amaurosis 9, MIM# 608553 to NMNAT1-related retinopathy MONDO:0800101; Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260; Leber congenital amaurosis 9, MIM# 608553
Mendeliome v1.3448 NOG Zornitza Stark Phenotypes for gene: NOG were changed from Brachydactyly, type B2 - MIM#611377; Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570) to NOG-related symphalangism spectrum disorder MONDO:0100521
Mendeliome v1.3447 NPHP3 Sangavi Sivagnanasundram reviewed gene: NPHP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 12872122, 19177160; Phenotypes: Nephronophthisis MONDO:0019005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3447 NPHP1 Sangavi Sivagnanasundram reviewed gene: NPHP1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 1 MONDO:0009728; Mode of inheritance: None
Mendeliome v1.3447 NOTCH2 Sangavi Sivagnanasundram reviewed gene: NOTCH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Acroosteolysis dominant type MONDO:0007057, Alagille syndrome MONDO:0007318; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3447 NOG Sangavi Sivagnanasundram reviewed gene: NOG: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: NOG-related symphalangism spectrum disorder MONDO:0100521; Mode of inheritance: None
Mendeliome v1.3447 NMNAT1 Sangavi Sivagnanasundram reviewed gene: NMNAT1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: NMNAT1-related retinopathy MONDO:0800101; Mode of inheritance: None
Mendeliome v1.3447 NLRC4 Sangavi Sivagnanasundram reviewed gene: NLRC4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: periodic fever-infantile enterocolitis-autoinflammatory syndrome MONDO:0014472; Mode of inheritance: None
Mendeliome v1.3447 NKX2-1 Sangavi Sivagnanasundram edited their review of gene: NKX2-1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3447 NKX2-1 Sangavi Sivagnanasundram reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Mode of inheritance: None
Mendeliome v1.3447 TBCB Zornitza Stark Phenotypes for gene: TBCB were changed from Neurodevelopmental disorder, MONDO:0700092, TBCB-related to Neurodevelopmental disorder with behavioral abnormalities and childhood onset spastic paraplegia, MIM# 621382
Mendeliome v1.3446 TBCB Zornitza Stark reviewed gene: TBCB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with behavioral abnormalities and childhood onset spastic paraplegia, MIM# 621382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3446 SETD5 Zornitza Stark edited their review of gene: SETD5: Changed rating: GREEN
Mendeliome v1.3446 FSHR Lucy Spencer reviewed gene: FSHR: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Ovarian dysgenesis 1 MIM#233300, Ovarian hyperstimulation syndrome MIM#608115; Mode of inheritance: None
Mendeliome v1.3446 FOXE3 Lucy Spencer commented on gene: FOXE3
Mendeliome v1.3446 EXT2 Lucy Spencer reviewed gene: EXT2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Exostoses, multiple, type 2 MIM#133701; Mode of inheritance: None
Mendeliome v1.3446 RNH1 Lucy Spencer reviewed gene: RNH1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, acute, infection-induced, susceptibility to, 12 MIM#620461; Mode of inheritance: None
Mendeliome v1.3446 RMI2 Lucy Spencer reviewed gene: RMI2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Bloom syndrome MONDO:0008876, RMI2-related; Mode of inheritance: None
Mendeliome v1.3446 RLBP1 Lucy Spencer reviewed gene: RLBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: RLBP1-related retinopathy MONDO:0100444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3446 RIPK1 Lucy Spencer reviewed gene: RIPK1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammation with episodic fever and lymphadenopathy MIM#618852; Mode of inheritance: None
Mendeliome v1.3446 RING1 Lucy Spencer reviewed gene: RING1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RING1-related; Mode of inheritance: None
Mendeliome v1.3446 RIMS1 Lucy Spencer reviewed gene: RIMS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy MONDO:0015993, RIMS1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3446 RHOH Lucy Spencer reviewed gene: RHOH: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 129 MIM#618307; Mode of inheritance: None
Mendeliome v1.3446 TBX2 Zornitza Stark Marked gene: TBX2 as ready
Mendeliome v1.3446 TBX2 Zornitza Stark Added comment: Comment when marking as ready: Green for the association with skeletal disorder, Amber for association with deafness.
Mendeliome v1.3446 TBX2 Zornitza Stark Gene: tbx2 has been classified as Green List (High Evidence).
Mendeliome v1.3446 TBX2 Zornitza Stark Phenotypes for gene: TBX2 were changed from Vertebral anomalies and variable endocrine and T-cell dysfunction - MIM#618223 to Vertebral anomalies and variable endocrine and T-cell dysfunction - MIM#618223; Hearing loss disorder, MONDO:0005365, TBX2-related
Mendeliome v1.3445 TBX2 Zornitza Stark Classified gene: TBX2 as Green List (high evidence)
Mendeliome v1.3445 TBX2 Zornitza Stark Gene: tbx2 has been classified as Green List (High Evidence).
Mendeliome v1.3444 TBX2 Zornitza Stark Classified gene: TBX2 as Amber List (moderate evidence)
Mendeliome v1.3444 TBX2 Zornitza Stark Gene: tbx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3443 TBX2 Krithika Murali Classified gene: TBX2 as Green List (high evidence)
Mendeliome v1.3443 TBX2 Krithika Murali Gene: tbx2 has been classified as Green List (High Evidence).
Mendeliome v1.3442 TBX2 Krithika Murali edited their review of gene: TBX2: Added comment: PMID: 36733940 Rafeeq et al 2022 report a novel de novo nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in a child with chondrodysplasia and GDD. Skeletal features included spinal deformities, short limbs, metaphyseal and epiphyseal dysplasia, and bilateral developmental dislocation of the hip (DDH).

PMID: 35311234 Makitie et al 2022 report a three-generation Finnish family with autosomal dominant osteochondrodysplasia and empty sella. Affected individuals (age range 24-44 years) exhibited unusual codfish-shaped vertebrae, severe early-onset and debilitating osteoarthritis and an empty sella without endocrine abnormalities. Clinical characteristics also include mild dysmorphic features, reduced sitting height ratio, and obesity.; Changed rating: GREEN
Mendeliome v1.3442 SLC7A2 Zornitza Stark Marked gene: SLC7A2 as ready
Mendeliome v1.3442 SLC7A2 Zornitza Stark Gene: slc7a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3442 SLC7A2 Zornitza Stark Classified gene: SLC7A2 as Amber List (moderate evidence)
Mendeliome v1.3442 SLC7A2 Zornitza Stark Gene: slc7a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3441 SLC7A2 Zornitza Stark gene: SLC7A2 was added
gene: SLC7A2 was added to Mendeliome. Sources: Literature
founder tags were added to gene: SLC7A2.
Mode of inheritance for gene: SLC7A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A2 were set to 41015522
Phenotypes for gene: SLC7A2 were set to Leukodystrophy, MONDO:0019046, SLC7A2-related
Review for gene: SLC7A2 was set to AMBER
Added comment: RAVINE leukoencephalopathy (RLE) is a hereditary autosomal recessive disease characterized by typical clinical and radiological signs that has so far been observed only in patients of Reunionese origin. The term RAVINE is a French acronym for the main clinical features of the disease: Réunion, Anorexie, Vomissements Incoercibles, signes NEurologiques (Reunion, Anorexia, Intractable Vomiting, NEurological signs). Patients with RLE carry the IVS1-1778A>G mutation of the SLC7A2 gene in the homozygous state.

Onset is in infancy. Death typically occurs before the age of 28months in a very narrow time window (23.0±2.2months).

PMID 41015522 summarises data from 40 affected individuals.
Sources: Literature
Mendeliome v1.3440 AMOT Zornitza Stark Marked gene: AMOT as ready
Mendeliome v1.3440 AMOT Zornitza Stark Gene: amot has been classified as Red List (Low Evidence).
Mendeliome v1.3440 AMOT Zornitza Stark Classified gene: AMOT as Red List (low evidence)
Mendeliome v1.3440 AMOT Zornitza Stark Gene: amot has been classified as Red List (Low Evidence).
Mendeliome v1.3439 AMOT Zornitza Stark reviewed gene: AMOT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.3439 EIF3B Zornitza Stark Marked gene: EIF3B as ready
Mendeliome v1.3439 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Mendeliome v1.3439 EIF3B Zornitza Stark Classified gene: EIF3B as Green List (high evidence)
Mendeliome v1.3439 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Mendeliome v1.3438 EIF3B Zornitza Stark gene: EIF3B was added
gene: EIF3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3B were set to 41033306
Phenotypes for gene: EIF3B were set to Syndromic disease (MONDO:0002254), EIF3B-related
Review for gene: EIF3B was set to GREEN
Added comment: Fourteen individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Mendeliome v1.3437 EIF3A Zornitza Stark Marked gene: EIF3A as ready
Mendeliome v1.3437 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Mendeliome v1.3437 EIF3A Zornitza Stark Classified gene: EIF3A as Green List (high evidence)
Mendeliome v1.3437 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Mendeliome v1.3436 EIF3A Zornitza Stark gene: EIF3A was added
gene: EIF3A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3A were set to 41033306
Phenotypes for gene: EIF3A were set to Syndromic disease (MONDO:0002254), EIF3A-related
Review for gene: EIF3A was set to GREEN
Added comment: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Mendeliome v1.3435 SF1 Zornitza Stark Marked gene: SF1 as ready
Mendeliome v1.3435 SF1 Zornitza Stark Gene: sf1 has been classified as Green List (High Evidence).
Mendeliome v1.3435 SF1 Zornitza Stark Classified gene: SF1 as Green List (high evidence)
Mendeliome v1.3435 SF1 Zornitza Stark Gene: sf1 has been classified as Green List (High Evidence).
Mendeliome v1.3434 MDGA2 Zornitza Stark Marked gene: MDGA2 as ready
Mendeliome v1.3434 MDGA2 Zornitza Stark Gene: mdga2 has been classified as Green List (High Evidence).
Mendeliome v1.3434 MDGA2 Zornitza Stark Classified gene: MDGA2 as Green List (high evidence)
Mendeliome v1.3434 MDGA2 Zornitza Stark Gene: mdga2 has been classified as Green List (High Evidence).
Mendeliome v1.3433 WNT4 Zornitza Stark Publications for gene: WNT4 were set to 22503279; 21377155; 16959810; 18179883; 15317892; 18182450
Mendeliome v1.3432 WNT4 Zornitza Stark edited their review of gene: WNT4: Changed publications: 22503279, 21377155, 16959810, 18179883, 15317892, 18182450, 40992710
Mendeliome v1.3432 WNT4 Zornitza Stark commented on gene: WNT4: Biallelic variants in WNT4 have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses.

PMID 40992710 reports second affected family, consanguineous, which had an affected fetus with CDH and an affected child had orofacial clefting.

A subset of Wnt4 null mouse embryos had perimembranous VSDs, anterior and posterior sac CDH, and soft palate clefts.

Bi-allelic association: two consanguineous families and a mouse model, maintain AMBER rating.
Mendeliome v1.3432 PDIA6 Zornitza Stark Phenotypes for gene: PDIA6 were changed from Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes to multiple congenital anomalies, MONDO:0019042, PDIA6-related
Mendeliome v1.3431 PDIA6 Zornitza Stark Publications for gene: PDIA6 were set to
Mendeliome v1.3430 PDIA6 Zornitza Stark Classified gene: PDIA6 as Green List (high evidence)
Mendeliome v1.3430 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Green List (High Evidence).
Mendeliome v1.3429 MIA3 Zornitza Stark Publications for gene: MIA3 were set to 32101163; 33778321
Mendeliome v1.3428 MIA3 Zornitza Stark Classified gene: MIA3 as Green List (high evidence)
Mendeliome v1.3428 MIA3 Zornitza Stark Gene: mia3 has been classified as Green List (High Evidence).
Mendeliome v1.3427 CASP8 Zornitza Stark Publications for gene: CASP8 were set to 12353035; 25814141; 12654726; 17213198; 16148088
Mendeliome v1.3426 CASP8 Zornitza Stark Classified gene: CASP8 as Green List (high evidence)
Mendeliome v1.3426 CASP8 Zornitza Stark Gene: casp8 has been classified as Green List (High Evidence).
Mendeliome v1.3425 CASP8 Zornitza Stark Tag founder tag was added to gene: CASP8.
Mendeliome v1.3425 CASP8 Zornitza Stark edited their review of gene: CASP8: Added comment: Additional individual reported, bring up total to 7 individuals from 5 families. All had the same homozygous missense variant, p.Arg265Trp. Some known to be distantly related. CIDP was a common manifestation.

GREEN but any variants apart from the founder variant should be treated with caution.; Changed rating: GREEN; Changed publications: 41026346; Changed phenotypes: Autoimmune lymphoproliferative syndrome, type IIB MIM#607271; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3425 PTBP1 Zornitza Stark Phenotypes for gene: PTBP1 were changed from to Neurodevelopmental disorder (MONDO:0700092), PTBP1-related
Mendeliome v1.3424 PTBP1 Zornitza Stark Publications for gene: PTBP1 were set to
Mendeliome v1.3423 PTBP1 Zornitza Stark Mode of inheritance for gene: PTBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3422 PTBP1 Zornitza Stark Classified gene: PTBP1 as Green List (high evidence)
Mendeliome v1.3422 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Green List (High Evidence).
Mendeliome v1.3421 CACNB1 Zornitza Stark Phenotypes for gene: CACNB1 were changed from Malignant hyperthermia susceptibility, MONDO:0800188, CACNB1-related to Congenital muscular dystrophy MONDO:0020121; Malignant hyperthermia susceptibility, MONDO:0800188, CACNB1-related
Mendeliome v1.3420 CACNB1 Zornitza Stark Publications for gene: CACNB1 were set to 27832566; 8943043; 29212769
Mendeliome v1.3419 CACNB1 Zornitza Stark Mode of inheritance for gene: CACNB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3418 CACNB1 Zornitza Stark Classified gene: CACNB1 as Amber List (moderate evidence)
Mendeliome v1.3418 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3417 ZDHHC18 Zornitza Stark Marked gene: ZDHHC18 as ready
Mendeliome v1.3417 ZDHHC18 Zornitza Stark Gene: zdhhc18 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3417 SWSAP1 Zornitza Stark Marked gene: SWSAP1 as ready
Mendeliome v1.3417 SWSAP1 Zornitza Stark Gene: swsap1 has been classified as Red List (Low Evidence).
Mendeliome v1.3417 SWSAP1 Zornitza Stark Classified gene: SWSAP1 as Red List (low evidence)
Mendeliome v1.3417 SWSAP1 Zornitza Stark Gene: swsap1 has been classified as Red List (Low Evidence).
Mendeliome v1.3416 FAP Zornitza Stark Marked gene: FAP as ready
Mendeliome v1.3416 FAP Zornitza Stark Gene: fap has been classified as Red List (Low Evidence).
Mendeliome v1.3416 FAP Zornitza Stark Classified gene: FAP as Red List (low evidence)
Mendeliome v1.3416 FAP Zornitza Stark Gene: fap has been classified as Red List (Low Evidence).
Mendeliome v1.3415 NFXL1 Zornitza Stark Marked gene: NFXL1 as ready
Mendeliome v1.3415 NFXL1 Zornitza Stark Gene: nfxl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3415 NFXL1 Zornitza Stark Classified gene: NFXL1 as Amber List (moderate evidence)
Mendeliome v1.3415 NFXL1 Zornitza Stark Gene: nfxl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3414 ZSWIM7 Zornitza Stark Marked gene: ZSWIM7 as ready
Mendeliome v1.3414 ZSWIM7 Zornitza Stark Gene: zswim7 has been classified as Green List (High Evidence).
Mendeliome v1.3414 ZSWIM7 Zornitza Stark Classified gene: ZSWIM7 as Green List (high evidence)
Mendeliome v1.3414 ZSWIM7 Zornitza Stark Gene: zswim7 has been classified as Green List (High Evidence).
Mendeliome v1.3413 PTBP2 Zornitza Stark Marked gene: PTBP2 as ready
Mendeliome v1.3413 PTBP2 Zornitza Stark Gene: ptbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3413 PTBP2 Zornitza Stark Classified gene: PTBP2 as Amber List (moderate evidence)
Mendeliome v1.3413 PTBP2 Zornitza Stark Gene: ptbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3412 KLK15 Zornitza Stark Marked gene: KLK15 as ready
Mendeliome v1.3412 KLK15 Zornitza Stark Gene: klk15 has been classified as Red List (Low Evidence).
Mendeliome v1.3412 KLK15 Zornitza Stark Classified gene: KLK15 as Red List (low evidence)
Mendeliome v1.3412 KLK15 Zornitza Stark Gene: klk15 has been classified as Red List (Low Evidence).
Mendeliome v1.3411 KLK15 Zornitza Stark reviewed gene: KLK15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3411 INCENP Zornitza Stark Marked gene: INCENP as ready
Mendeliome v1.3411 INCENP Zornitza Stark Gene: incenp has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3411 INCENP Zornitza Stark Classified gene: INCENP as Amber List (moderate evidence)
Mendeliome v1.3411 INCENP Zornitza Stark Gene: incenp has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3410 GSTZ1 Zornitza Stark Marked gene: GSTZ1 as ready
Mendeliome v1.3410 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Green List (High Evidence).
Mendeliome v1.3410 GSTZ1 Zornitza Stark Classified gene: GSTZ1 as Green List (high evidence)
Mendeliome v1.3410 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Green List (High Evidence).
Mendeliome v1.3409 FSIP2 Zornitza Stark Marked gene: FSIP2 as ready
Mendeliome v1.3409 FSIP2 Zornitza Stark Gene: fsip2 has been classified as Green List (High Evidence).
Mendeliome v1.3409 FSIP2 Zornitza Stark Classified gene: FSIP2 as Green List (high evidence)
Mendeliome v1.3409 FSIP2 Zornitza Stark Gene: fsip2 has been classified as Green List (High Evidence).
Mendeliome v1.3408 CDK9 Zornitza Stark Marked gene: CDK9 as ready
Mendeliome v1.3408 CDK9 Zornitza Stark Gene: cdk9 has been classified as Green List (High Evidence).
Mendeliome v1.3407 ABCB4 Chirag Patel Publications for gene ABCB4 were changed from 8666348; 17726488; 18482588; 28924228; 32376413; 9419367; 26474921; 32793533; 11313315 to 8666348; 17726488; 18482588; 28924228; 32376413; 9419367; 26474921; 32793533; 11313315
Mendeliome v1.3406 ABCB4 Chirag Patel Source Victorian Clinical Genetics Services was removed from ABCB4.
Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803) to Progressive familial intrahepatic cholestasis type 3, MONDO:0011214; Cholestasis, intrahepatic, of pregnancy, 3 MIM#614972; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803)
Mendeliome v1.3405 ABCC8 Chirag Patel Source Victorian Clinical Genetics Services was removed from ABCC8.
Source Expert list was added to ABCC8.
Phenotypes for gene: ABCC8 were changed from Maturity-onset diabetes of the young, type 12, MIM# 621196; Diabetes mellitus, noninsulin-dependent MIM#125853; Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857; Diabetes mellitus, transient neonatal 2 MIM#610374; Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450; Hypoglycemia of infancy, leucine-sensitive MIM#240800 to Maturity-onset diabetes of the young, type 12, MIM# 621196; Diabetes mellitus, noninsulin-dependent MIM#125853; Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857; Diabetes mellitus, transient neonatal 2 MIM#610374; Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450; Hypoglycemia of infancy, leucine-sensitive MIM#240800; Pulmonary arterial hypertension, MONDO:0015924, ABCC8-related
Publications for gene ABCC8 were changed from 21054355, 32027066, 32376986, 30354297, 35811711, 32934261, 31727138 to 21054355, 32027066, 32376986, 30354297, 35811711, 32934261, 31727138
Mendeliome v1.3404 AGTPBP1 Chirag Patel Phenotypes for gene: AGTPBP1 were changed from Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276 to Neurodegeneration, childhood-onset, with cerebellar atrophy, MONDO:0032650
Publications for gene AGTPBP1 were changed from 30420557, 28600779, 30976113, 38153683, 28325758 to 30420557, 28600779, 30976113, 38153683, 28325758
Mendeliome v1.3403 ATP1A3 Chirag Patel Source Victorian Clinical Genetics Services was removed from ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Alternating hemiplegia of childhood 2, MIM# 614820; CAPOS syndrome, MIM# 601338; Dystonia-12, MIM# 128235; Polymicrogyria to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Mendeliome v1.3402 ALS2 Chirag Patel Source Literature was removed from ALS2.
Source ClinGen was added to ALS2.
Phenotypes for gene: ALS2 were changed from Infantile onset ascending spastic paralysis (MIM#607225); Juvenile amyotrophic lateral sclerosis 2 (MIM#205100); Juvenile primary lateral sclerosis (MIM#606353) to ALS2-related motor neuron disease, MONDO:0100227
Publications for gene ALS2 were changed from 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358 to 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358
Mendeliome v1.3401 ALG14 Chirag Patel Source Victorian Clinical Genetics Services was removed from ALG14.
Source Expert list was added to ALG14.
Publications for gene ALG14 were changed from 30221345, 23404334, 28733338, 33751823, 34971077 to 30221345, 23404334, 28733338, 33751823, 34971077
Mendeliome v1.3400 AGK Chirag Patel Source Victorian Clinical Genetics Services was removed from AGK.
Source Expert list was added to AGK.
Mendeliome v1.3399 DHX9 Chirag Patel Source Literature was removed from DHX9.
Source Expert list was added to DHX9.
Phenotypes for gene: DHX9 were changed from Intellectual developmental disorder, autosomal dominant 75, MIM# 620988; Charcot-Marie-Tooth disease, MONDO:0015626 to Intellectual developmental disorder, autosomal dominant 75, MIM# 620988; Charcot-Marie-Tooth disease, MONDO:0015626, DHX9-related
Mendeliome v1.3398 DGUOK Chirag Patel Source Victorian Clinical Genetics Services was removed from DGUOK.
Source ClinGen was added to DGUOK.
Publications for gene DGUOK were changed from 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938 to 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938
Mendeliome v1.3397 DHH Chirag Patel Classified gene: DHH as Green List (high evidence)
Mendeliome v1.3397 DHH Chirag Patel Gene: dhh has been classified as Green List (High Evidence).
Mendeliome v1.3396 DHH Chirag Patel Source Victorian Clinical Genetics Services was removed from DHH.
Source Expert list was added to DHH.
Phenotypes for gene: DHH were changed from 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080; 46XY sex reversal 7 MIM#233420 to 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome, MONDO:0011766
Rating Changed from Green List (high evidence) to Red List (low evidence)
Mendeliome v1.3394 DNAJC6 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAJC6.
Source Expert list was added to DNAJC6.
Publications for gene DNAJC6 were changed from 22563501, 23211418, 26528954, 33983693 to 22563501, 23211418, 26528954, 33983693
Mendeliome v1.3393 DNAH8 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAH8.
Source ClinGen was added to DNAH8.
Phenotypes for gene: DNAH8 were changed from Spermatogenic failure 46, MIM#619095; Asthenozoospermia; primary ciliary dyskinesia to Spermatogenic failure 46, MONDO:0033673; Primary ciliary dyskinesia, MONDO:0016575, DNAH8-related
Publications for gene DNAH8 were changed from 31178125, 32619401, 32681648, 33704367, 24307375 to 31178125, 32619401, 32681648, 33704367, 24307375
Mendeliome v1.3392 DNAH1 Chirag Patel Classified gene: DNAH1 as Green List (high evidence)
Mendeliome v1.3392 DNAH1 Chirag Patel Gene: dnah1 has been classified as Green List (High Evidence).
Mendeliome v1.3391 DNAH1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAH1.
Source ClinGen was added to DNAH1.
Phenotypes for gene: DNAH1 were changed from primary ciliary dyskinesia,37 MIM#617577; Spermatogenic failure 18 MIM#617576 to Spermatogenic failure 18, MONDO:0054615; Primary ciliary dyskinesia 7, MONDO:0012748
Publications for gene DNAH1 were changed from 34867808, 31507630, 24360805, 27798045, 11371505, 27798045, 29449551, 25927852, 31765523, 33577779, 34210339 to 34867808, 31507630, 24360805, 27798045, 11371505, 27798045, 29449551, 25927852, 31765523, 33577779, 34210339
Rating Changed from Green List (high evidence) to Red List (low evidence)
Mendeliome v1.3390 DHCR24 Chirag Patel Source Victorian Clinical Genetics Services was removed from DHCR24.
Phenotypes for gene: DHCR24 were changed from Desmosterolosis MIM#602398; Disorders of the metabolism of sterols to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Mendeliome v1.3389 DEF6 Chirag Patel Phenotypes for gene: DEF6 were changed from Immunodeficiency 87 and autoimmunity, MIM# 619573; Systemic autoimmunity to Immunodeficiency 87 and autoimmunity, MONDO:0030457
Mendeliome v1.3388 DDX11 Chirag Patel Source Victorian Clinical Genetics Services was removed from DDX11.
Source ClinGen was added to DDX11.
Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM# 613398; MONDO:0013252 to Warsaw breakage syndrome, MONDO:0013252
Publications for gene DDX11 were changed from 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203 to 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203
Mendeliome v1.3387 DDHD1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DDHD1.
Source ClinGen was added to DDHD1.
Phenotypes for gene: DDHD1 were changed from Spastic paraplegia 28, autosomal recessive, 609340; MONDO:0012256 to Hereditary spastic paraplegia 28, MONDO:0012256
Publications for gene DDHD1 were changed from 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578 to 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578
Mendeliome v1.3386 DCLRE1C Chirag Patel Source Victorian Clinical Genetics Services was removed from DCLRE1C.
Source Expert list was added to DCLRE1C.
Phenotypes for gene: DCLRE1C were changed from Severe combined immunodeficiency, Athabascan type MIM# 602450; Omenn syndrome, MIM# 603554 to Severe combined immunodeficiency due to DCLRE1C deficiency, MONDO:0011225
Publications for gene DCLRE1C were changed from 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179 to 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179
Mendeliome v1.3385 DCDC2 Chirag Patel Source Victorian Clinical Genetics Services was removed from DCDC2.
Source Victorian Clinical Genetics Services was removed from DCDC2.
Source Expert list was added to DCDC2.
Phenotypes for gene: DCDC2 were changed from Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394 to Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394; Deafness, autosomal recessive 66, MIM# 610212
Mendeliome v1.3384 DBR1 Chirag Patel Publications for gene DBR1 were changed from 39023559, 29474921, 37656279 to 39023559, 29474921, 37656279
Mendeliome v1.3383 DNM2 Chirag Patel Publications for gene DNM2 were changed from 15731758; 17636067; 33459893; 31628461; 23092955; 16227997; 33458580; 30232666; 24465259; 23938035 to 15731758; 17636067; 33459893; 31628461; 23092955; 16227997; 33458580; 30232666; 24465259; 23938035
Mendeliome v1.3382 MAFA Sangavi Sivagnanasundram gene: MAFA was added
gene: MAFA was added to Mendeliome. Sources: Other
Mode of inheritance for gene: MAFA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAFA were set to 29339498
Phenotypes for gene: MAFA were set to Insulinomatosis and diabetes mellitus, OMIM #:147630
Review for gene: MAFA was set to GREEN
Added comment: Addition of this review to Mendeliome, was only on the hyperinsulinism panel

2 families with 36 individuals with AD inheritance of diabetes mellitus or insulinomatosis (adult-onset recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumours of pancreas). WES identified the same missense MAFA mutation (p.Ser64Phe, c.191C>T) segregating with both phenotypes of insulinomatosis and diabetes in both families. The p.Ser64Phe mutation was found to impair phosphorylation within the transactivation domain of MAFA and profoundly increased MAFA protein stability under both high and low glucose concentrations in β-cell lines. In addition, the transactivation potential of p.Ser64Phe MAFA in β-cell lines was enhanced compared with wild-type MAFA. The human phenotypes associated with the p.Ser64Phe MAFA missense mutation reflect both the oncogenic capacity of MAFA and its key role in islet β-cell activity.
Sources: Other
Mendeliome v1.3382 DHX38 Arina Puzriakova changed review comment from: - PMID: 35719279 (2022) - another consanguineous family from Saudi Arabia with two sisters presented affected by retinitis pigmentosa since childhood. Whole exome sequencing identified a missense homozygous variant (c.2571C>T, p.(Ala857=)) in the DHX38 gene which segregated with the phenotype. No functional studies performed.

PMID: 37867960 (2023) - zebrafish knockout model shows a role in the development of the retina; to: - PMID: 35719279 (2022) - another consanguineous family from Saudi Arabia with two sisters presented affected by retinitis pigmentosa since childhood. Whole exome sequencing identified a missense homozygous variant (c.2571C>T, p.(Ala857=)) in the DHX38 gene which segregated with the phenotype. No functional studies performed.

- PMID: 37867960 (2023) - zebrafish knockout model shows a role in the development of the retina
Mendeliome v1.3382 DHX38 Arina Puzriakova reviewed gene: DHX38: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3382 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Mendeliome v1.3381 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Mendeliome v1.3381 INCENP Rylee Peters gene: INCENP was added
gene: INCENP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: INCENP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INCENP were set to 41005306
Phenotypes for gene: INCENP were set to Oocyte/zygote/embryo maturation arrest MONDO:0014769, INCENP-related
Review for gene: INCENP was set to AMBER
Added comment: 3 unrelated women presenting with abnormal oocyte morphology and/or low fertilisation rate from a large cohort of 3627 individuals. WES identified biallelic missense variants:
R267Q (gnomAD v4: 1717 hets, 12 homs), R280W (5 hets, 0 homs), P444L (207 hets, 0 homs), R693W (686 hets, 1 hom), K816T (110 hets, 1 hom), K890E (3 hets, 0 homs).

siRNA-mediated knock-down of INCENP in mouse oocytes reduced polar-body extrusion rates, demonstrating that loss of function of the protein affects oocyte maturation.
Sources: Literature
Mendeliome v1.3381 ANKRD24 Rylee Peters reviewed gene: ANKRD24: Rating: RED; Mode of pathogenicity: None; Publications: 40989574; Phenotypes: Sensorineural hearing loss disorder MONDO:0020678, ANKRD24-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3381 SWSAP1 Rylee Peters gene: SWSAP1 was added
gene: SWSAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SWSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SWSAP1 were set to 40991243
Phenotypes for gene: SWSAP1 were set to Primary ovarian insufficiency, MONDO:0005387, SWSAP1-related
Review for gene: SWSAP1 was set to RED
Added comment: Cohort with severe isolated premature ovarian insufficiency. 1x individual homozygous for a frameshift SWSAP1 variant, c.353del, p.(Gly118AlafsTer2), absent from gnomAD v4.

Functional: western-blot indicates reduced stability of the truncated protein; the truncated SWSAP1 variant fails to complement the IH-HR (interhomolog homologous recombination) defect of Swsap1−/− cells (undetected IH-HR activity).
Sources: Literature
Mendeliome v1.3381 FSIP2 Rylee Peters gene: FSIP2 was added
gene: FSIP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FSIP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FSIP2 were set to 30137358; 40968718; 36632462; 33631238
Phenotypes for gene: FSIP2 were set to Spermatogenic failure 34, MIM#618153
Review for gene: FSIP2 was set to GREEN
Added comment: Multiple unrelated cases with multiple morphological abnormalities of the sperm flagella (MMAF) carrying biallelic variants.
Sources: Literature
Mendeliome v1.3381 AMOT Rylee Peters gene: AMOT was added
gene: AMOT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AMOT was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AMOT were set to 40892511
Phenotypes for gene: AMOT were set to Congenital hydrocephalus MONDO:0016349, AMOT-related
Review for gene: AMOT was set to AMBER
Added comment: 1x family with isolated X-linked congenital hydrocephalus – clinical presentation considered late, identified in the third trimester. Variant segregated with disease in 6x affected hemizygous males (4x live-born and 2x terminated male fetuses). Carrier females are apparently normal (no brain MRI was performed).

Exome sequencing identified start loss variant, c.2T>C p.(Met1Thr). Functional analyses identify that the variant results in a protein lacking 91 amino acids from the N-terminus and leads to abnormally increased AMOT protein levels (increased stability due to loss of degradation signals), which disrupts epithelial and endothelial barrier integrity.
Sources: Literature
Mendeliome v1.3381 HECTD4 Elena Savva reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28191890, 31981491, 31785789; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3381 MDGA2 Sangavi Sivagnanasundram changed review comment from: Affected individuals present with a broad neurodevelopmental impairment phenotype.

Pre-print - https://doi.org/10.1101/2025.08.28.25330873
Individuals with developmental and epileptic encephalopathy (DEE)
8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features.
7 different biallelic LoF variants were identified
p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1
In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism.

PMID: 40168357, 27608760
A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment).
The mice also showed abnormalities in excitatory synapses.
Sources: Other; to: Affected individuals present with a broad neurodevelopmental impairment-like phenotype.

Pre-print - https://doi.org/10.1101/2025.08.28.25330873
Individuals with developmental and epileptic encephalopathy (DEE)
8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features.
7 different biallelic LoF variants were identified
p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1
In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism.

PMID: 40168357, 27608760
A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment).
The mice also showed abnormalities in excitatory synapses.
Sources: Other
Mendeliome v1.3381 MDGA2 Sangavi Sivagnanasundram gene: MDGA2 was added
gene: MDGA2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: MDGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDGA2 were set to https://doi.org/10.1101/2025.08.28.25330873; 40168357; 27608760
Phenotypes for gene: MDGA2 were set to MDGA2-related neurodevelopmental disorder MONDO:0700092
Review for gene: MDGA2 was set to GREEN
Added comment: Affected individuals present with a broad neurodevelopmental impairment phenotype.

Pre-print - https://doi.org/10.1101/2025.08.28.25330873
Individuals with developmental and epileptic encephalopathy (DEE)
8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features.
7 different biallelic LoF variants were identified
p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1
In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism.

PMID: 40168357, 27608760
A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment).
The mice also showed abnormalities in excitatory synapses.
Sources: Other
Mendeliome v1.3381 CACNB1 Sangavi Sivagnanasundram reviewed gene: CACNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 41023410; Phenotypes: Congenital muscular dystrophy MONDO:0020121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3381 ATP5O Bryony Thompson Tag new gene name tag was added to gene: ATP5O.
Mendeliome v1.3381 DDOST Bryony Thompson Phenotypes for gene: DDOST were changed from Congenital disorder of glycosylation, type Ir, MIM# 614507 to DDOST-congenital disorder of glycosylation MONDO:0013789; inherited oocyte maturation defect MONDO:0014769
Mendeliome v1.3380 DDOST Bryony Thompson Publications for gene: DDOST were set to 22305527
Mendeliome v1.3379 DDOST Bryony Thompson Classified gene: DDOST as Green List (high evidence)
Mendeliome v1.3379 DDOST Bryony Thompson Gene: ddost has been classified as Green List (High Evidence).
Mendeliome v1.3378 DDOST Bryony Thompson reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 22305527, 34462534, 36214423, 37848450, 33413482, 36631682, 41005306; Phenotypes: DDOST-congenital disorder of glycosylation MONDO:0013789, inherited oocyte maturation defect MONDO:0014769; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3378 MIA3 Sangavi Sivagnanasundram reviewed gene: MIA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40948380, 40119123; Phenotypes: odontochondrodysplasia MONDO:0031169; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3378 RYR3 Bryony Thompson Classified gene: RYR3 as Green List (high evidence)
Mendeliome v1.3378 RYR3 Bryony Thompson Gene: ryr3 has been classified as Green List (High Evidence).
Mendeliome v1.3377 RYR3 Bryony Thompson Phenotypes for gene: RYR3 were changed from Congenital myopathy 20, MIM# 620310; developmental and epileptic encephalopathy (MONDO:0100062) to congenital heart disease MONDO:0005453; Congenital myopathy 20, MIM# 620310; developmental and epileptic encephalopathy (MONDO:0100062)
Mendeliome v1.3376 RYR3 Bryony Thompson Publications for gene: RYR3 were set to 29498452; 32451403; 31230720; 25262651
Mendeliome v1.3375 RYR3 Bryony Thompson reviewed gene: RYR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 39762984, 41022857, 39840699, 39220738, 25262651, 29667327; Phenotypes: congenital heart disease MONDO:0005453, developmental and epileptic encephalopathy MONDO:0100062; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3375 ZDHHC18 Bryony Thompson Classified gene: ZDHHC18 as Amber List (moderate evidence)
Mendeliome v1.3375 ZDHHC18 Bryony Thompson Gene: zdhhc18 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3374 ZDHHC18 Bryony Thompson changed review comment from: ZDHHC18 appears among significant CHD genes in the de novo enrichment analysis. Two de novo missense variants (W290L, G297A) were identified in 2 probands via trio analysis in a CHD cohort.
Sources: Literature; to: ZDHHC18 appears among significant CHD genes in the de novo enrichment analysis. Two de novo missense variants (W290L, G297A) were identified in 2 probands via trio analysis in a CHD cohort. No functional assays conducted.
Sources: Literature
Mendeliome v1.3374 ZDHHC18 Bryony Thompson gene: ZDHHC18 was added
gene: ZDHHC18 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZDHHC18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZDHHC18 were set to 41022857
Phenotypes for gene: ZDHHC18 were set to congenital heart disease MONDO:0005453
Review for gene: ZDHHC18 was set to AMBER
Added comment: ZDHHC18 appears among significant CHD genes in the de novo enrichment analysis. Two de novo missense variants (W290L, G297A) were identified in 2 probands via trio analysis in a CHD cohort.
Sources: Literature
Mendeliome v1.3373 TM2D3 Zornitza Stark Phenotypes for gene: TM2D3 were changed from Neurodevelopmental disorder, MONDO:0700092, TM2D3-related to Neurocardiorenal malformation syndrome, MIM# 621379
Mendeliome v1.3372 TM2D3 Zornitza Stark edited their review of gene: TM2D3: Changed phenotypes: Neurocardiorenal malformation syndrome, MIM# 621379
Mendeliome v1.3372 ATXN7L3 Zornitza Stark Phenotypes for gene: ATXN7L3 were changed from Neurodevelopmental disorder, MONDO_0100500, ATXN7L3-related to Harel-Tora neurodevelopmental syndrome, MIM# 621377
Mendeliome v1.3371 ATXN7L3 Zornitza Stark reviewed gene: ATXN7L3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Harel-Tora neurodevelopmental syndrome, MIM# 621377; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3371 NAMPT Bryony Thompson Marked gene: NAMPT as ready
Mendeliome v1.3371 NAMPT Bryony Thompson Gene: nampt has been classified as Red List (Low Evidence).
Mendeliome v1.3371 NAMPT Bryony Thompson gene: NAMPT was added
gene: NAMPT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAMPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAMPT were set to 41004591
Phenotypes for gene: NAMPT were set to hereditary motor and sensory neuropathy MONDO:0015358
Review for gene: NAMPT was set to RED
Added comment: A single family reported.
Disease Context: sensory and motor neuropathy with motor coordination impairment, muscle atrophy/weakness, foot/hand deformities, loss of sensation and positive Babinski sign
Families: 1 family
Patients: 2
Phenotype: impaired motor coordination, muscle atrophy/weakness, foot and hand deformities, diminished sensation, positive Babinski sign
Mode of inheritance: Biallelic (autosomal recessive; parents heterozygous carriers, affected siblings homozygous). No mention of consanguinity
Variants: c.472G>C (p.P158A) (missense)
Population Frequency: gnomAD: 0
Segregation: parents heterozygous, both affected siblings homozygous (pedigree confirmed)
Functional Studies: recombinant NAMPT protein activity assay; thermal shift stability assay; patient fibroblast bioenergetic, mitochondrial and oxidative stress assays; CRISPR‑generated isogenic fibroblasts; homozygous p.P158A mouse model showing metabolic, synaptic and motor neuron defects; rescue with NMN/P7C3
Prior Reports: none.
Sources: Literature
Mendeliome v1.3370 DBX1 Bryony Thompson Marked gene: DBX1 as ready
Mendeliome v1.3370 DBX1 Bryony Thompson Gene: dbx1 has been classified as Red List (Low Evidence).
Mendeliome v1.3370 DBX1 Bryony Thompson gene: DBX1 was added
gene: DBX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DBX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBX1 were set to 40995053
Phenotypes for gene: DBX1 were set to central hypoventilation syndrome, congenital MONDO:0800031
Review for gene: DBX1 was set to RED
Added comment: Disease Context: Congenital central hypoventilation syndrome (atypical CCHS) with central hypotonia, global developmental delay, seizures, autoaggressive behavior
Families: 1 (1 unrelated)
Patients: 1
Phenotype: congenital central hypoventilation, central hypotonia, global developmental delay, seizures, autoaggressive behavior
Mode of inheritance: Biallelic (consanguineous parents (first cousins))
Variants: c.340_341delGC (frameshift)
Population Frequency: NR
Segregation: NR
Functional Studies: mouse Dbx1 knockout lethality indicating essential role in respiration
Prior Reports: 0
Sources: Literature
Mendeliome v1.3369 TRIM49 Bryony Thompson Marked gene: TRIM49 as ready
Mendeliome v1.3369 TRIM49 Bryony Thompson Gene: trim49 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3369 TRIM49 Bryony Thompson Classified gene: TRIM49 as Amber List (moderate evidence)
Mendeliome v1.3369 TRIM49 Bryony Thompson Gene: trim49 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3368 TRIM49 Bryony Thompson changed review comment from: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not (Box 438, Box 440, Box 439). This constitutes convincing functional evidence for pathogenicity in two families.
Sources: Literature; to: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not. This constitutes convincing functional evidence for pathogenicity in two families.
Sources: Literature
Mendeliome v1.3368 TRIM49 Bryony Thompson gene: TRIM49 was added
gene: TRIM49 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM49 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM49 were set to 40956390
Phenotypes for gene: TRIM49 were set to retinitis pigmentosa MONDO:0019200
Review for gene: TRIM49 was set to AMBER
Added comment: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not (Box 438, Box 440, Box 439). This constitutes convincing functional evidence for pathogenicity in two families.
Sources: Literature
Mendeliome v1.3367 PCDHA9 Bryony Thompson Marked gene: PCDHA9 as ready
Mendeliome v1.3367 PCDHA9 Bryony Thompson Gene: pcdha9 has been classified as Red List (Low Evidence).
Mendeliome v1.3367 PCDHA9 Bryony Thompson gene: PCDHA9 was added
gene: PCDHA9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCDHA9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCDHA9 were set to 29477871; 40988636
Phenotypes for gene: PCDHA9 were set to Hirschsprung disease MONDO:0018309; root resorption MONDO:0001997
Review for gene: PCDHA9 was set to RED
Added comment: Single publication reporting an association with Hirschsprung disease, including a missense in a family (p.Gly572Arg) that is too common in gnomAD to be associated with disease and 2 rare missense in 2 sporadic cases. Knockdown in a cell line increased proliferation and
migration, but suppressed apoptosis. A single publication with a single missense reported in association with short root anomaly.
Sources: Literature
Mendeliome v1.3366 RNU6ATAC Zornitza Stark Marked gene: RNU6ATAC as ready
Mendeliome v1.3366 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Red List (Low Evidence).
Mendeliome v1.3366 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Red List (low evidence)
Mendeliome v1.3366 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Red List (Low Evidence).
Mendeliome v1.3365 HYPK Zornitza Stark Publications for gene: HYPK were set to Clinical Genetics Early View
Mendeliome v1.3364 DNAH14 Zornitza Stark reviewed gene: DNAH14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3364 TLN1 Zornitza Stark Publications for gene: TLN1 were set to 30888838; 35861643
Mendeliome v1.3363 BCAT1 Zornitza Stark Marked gene: BCAT1 as ready
Mendeliome v1.3363 BCAT1 Zornitza Stark Gene: bcat1 has been classified as Red List (Low Evidence).
Mendeliome v1.3363 BCAT1 Zornitza Stark Classified gene: BCAT1 as Red List (low evidence)
Mendeliome v1.3363 BCAT1 Zornitza Stark Gene: bcat1 has been classified as Red List (Low Evidence).
Mendeliome v1.3362 BCAT1 Lucy Spencer gene: BCAT1 was added
gene: BCAT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BCAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCAT1 were set to 41029903
Phenotypes for gene: BCAT1 were set to Neurodevelopmental disorder (MONDO:0700092), BCAT1-related
Review for gene: BCAT1 was set to RED
Added comment: PMID: 41029903 One patient with a suspected neurometabolic disorder; congenital blindness and suspected Leber Congenital Amaurosis, microcephaly, failure to thrive, profound global developmental delay and extensive delayed myelination on MRI. AT 10 he was non-verbal and non-ambulatory with regression of motor skills and -3SD for height and weight. Compound heterozygous for Phe264Leu (539 hets but no homs in gnomad v4) and Glu348Lys (over 8000 hets and 24 homs in gnomad v4).

in compound heterozygous iPSCs a severe 75% reduction in BCAT1 protein levels was seen, but mRNA levels were normal suggesting the variants affect protein stability or increased degradation.
Sources: Literature
Mendeliome v1.3362 TLN1 Lucy Spencer edited their review of gene: TLN1: Added comment: PMID: 40960860 de novo L353F identified in a patient with increased nuchal translucency, leukopenia, thrombocytopenia, congenital cataracts, multiple episodes of acute bronchitis, skin lesions and swelling after exercise in cold weather. Overlapping authors with PMID: 35861643, and they are postulating this is a 2nd case of the condition reported there. Some functional studies showing decreased thermal stability, has slower cellular migration and that it was slightly more aggregation-prone than WT.

Shared symptoms between both patients; leukopenia, thrombocytopenia, congenital cataract, and recurring episodes of acute bronchitis. Both mutations situated in the talin-1 head F2F3 domains and both have been shown to have defects in cellular migration and integrin activation.; Changed rating: AMBER; Changed publications: 40960860; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3362 TLN1 Lucy Spencer reviewed gene: TLN1: Rating: RED; Mode of pathogenicity: None; Publications: 39704176; Phenotypes: Capillary leak syndrome MONDO:0001956, TLN1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.3362 DNAH14 Lucy Spencer reviewed gene: DNAH14: Rating: AMBER; Mode of pathogenicity: None; Publications: 36344539, 41002930; Phenotypes: Neurodevelopmental disorder MONDO:0700092, DNAH14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3362 HYPK Sangavi Sivagnanasundram reviewed gene: HYPK: Rating: ; Mode of pathogenicity: None; Publications: 40986405; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, HYPK-related; Mode of inheritance: None
Mendeliome v1.3362 RNU6ATAC Lucy Spencer gene: RNU6ATAC was added
gene: RNU6ATAC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU6ATAC were set to 40975062
Phenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related
Review for gene: RNU6ATAC was set to RED
Added comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC.
Sources: Literature
Mendeliome v1.3362 NFXL1 Lucy Spencer gene: NFXL1 was added
gene: NFXL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFXL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFXL1 were set to 40430072; 41024252
Phenotypes for gene: NFXL1 were set to Syndromic disease (MONDO:0002254), NFXL1-related
Review for gene: NFXL1 was set to AMBER
Added comment: PMID: 40430072 2 siblings with psychosis and schizophrenia, homozygous for Cys441Tyr. Some modelling suggested a deleterious affect but no functional studies performed.

PMID: 41024252 8 patients from 7 families with joint hyperlaxity, with or without short stature and renal disease. 6 families were homozygous for p.(Cys539Trpfs*64) while the other two were homozygous for p.(Lys681*). Paper described both as founder variants but they are rare/absent in gnomad.

Joint hyperlaxity (7), chronic kidney disease/FSGS (2) small echogenic kidneys (3), acute kidney injury (1), dysmorphic features (6), short stature (6), speech delay (3).

One patient also had epilepsy, developmental delay and spasticity however c.728+1G>A in WDR45 explained this part of her phenotype. Other patients also had more severe outlying symptoms with no other explanation mentioned: 1 with developmental delay, hearing loss, brain malformations, skeletal abnormalities, and another a 3 year old who passed away following a complex medical course including blue sclera, proximal tibial fracture, severe respiratory distress due to a chest infection, and acute kidney injury.

Amber given the variable phenotype findings of the reported patients and only 2 homozygous variants identified so far
Sources: Literature
Mendeliome v1.3362 PTBP1 Lucy Spencer changed review comment from: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%).

Various functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss
variants also leading to increased protein stability.; to: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%).

Variants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.

Various functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss
variants also leading to increased protein stability.
Mendeliome v1.3362 PTBP1 Lucy Spencer reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40965981; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), PTBP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3362 PTBP2 Lucy Spencer gene: PTBP2 was added
gene: PTBP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTBP2 were set to 40965981
Phenotypes for gene: PTBP2 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP2-related
Review for gene: PTBP2 was set to AMBER
Added comment: PMID: 40965981 2 males with developmental delay, ID, autistic features. 1 had some dysmorphic features and tonic-clonic seizures. both probands had a de novo variant in PTBP2 NM_021190.4:c.2T>C (p.Met1?) and NM_021190.4:c.41G>C (p.Arg14Thr), absent from gnomad. Transfection of the variants in transfection in NIH-3T3 cells showed the missense had cytoplasmic retention and colocalization with processing bodies, and that there were 2 alternative downstream start sites Met32 and Met35 that may be used instead.
Sources: Literature
Mendeliome v1.3362 GSTZ1 Lucy Spencer changed review comment from: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1 compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.

PMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.

PMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A variant showed it lead to the out of frame 10bp retention of the intron.
Sources: Literature; to: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1 compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.

PMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.

PMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A variant showed it lead to the out of frame 10bp retention of the intron. Val99Met has 1170 hets and 4 homs in gnomad, as this condition appears to be clinically benign this is not a concern.

Currently rated as moderate by ClinGen, the review does not include the most recent paper
Sources: Literature
Mendeliome v1.3362 GSTZ1 Lucy Spencer gene: GSTZ1 was added
gene: GSTZ1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GSTZ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSTZ1 were set to 27876694; 38535121; 41009955
Phenotypes for gene: GSTZ1 were set to Maleylacetoacetate isomerase deficiency MIM#617596
Review for gene: GSTZ1 was set to GREEN
Added comment: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1 compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.

PMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.

PMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A variant showed it lead to the out of frame 10bp retention of the intron.
Sources: Literature
Mendeliome v1.3362 ITGAV Zornitza Stark Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Mendeliome v1.3361 ITGAV Zornitza Stark Classified gene: ITGAV as Green List (high evidence)
Mendeliome v1.3361 ITGAV Zornitza Stark Gene: itgav has been classified as Green List (High Evidence).
Mendeliome v1.3360 ITGAV Zornitza Stark edited their review of gene: ITGAV: Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Mendeliome v1.3360 ITGAV Zornitza Stark edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372
Mendeliome v1.3360 UBR5 Zornitza Stark Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372
Mendeliome v1.3359 UBR5 Zornitza Stark reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None
Mendeliome v1.3359 CDK9 Bryony Thompson Classified gene: CDK9 as Green List (high evidence)
Mendeliome v1.3359 CDK9 Bryony Thompson Gene: cdk9 has been classified as Green List (High Evidence).
Mendeliome v1.3358 CDK9 Bryony Thompson gene: CDK9 was added
gene: CDK9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK9 were set to 40954203; 33640901; 30237576; 26633546
Phenotypes for gene: CDK9 were set to multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome MONDO:0015160; CHARGE-like syndrome with retinal dystrophy
Review for gene: CDK9 was set to GREEN
Added comment: Biallelic variants in at least six unrelated families:
1) proband that displays retinal dystrophy without a CHARGE-like malformation syndrome (c.862G>A/p.A288T + c.961C>T/p.P321S).
2) A boy with a phenotype resembling CHARGE syndrome (multiple anomalies involving the eyes, ears, cleft lip, and palate, and intellectual disability) with retinal dystrophy (p.A288T/p.R303C),
3-7) 4 consanguineous families homozygous for p.R225C, including a set of cousins.
CDK9 variants demonstrated decreased kinase activity. One of the studies suggested the extent the kinase activity is reduced may account for the absence/presence of the CHARGE-like phenotype with retinal dystrophy
Sources: Literature
Mendeliome v1.3357 DNMT1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNMT1.
Source ClinGen was added to DNMT1.
Source Literature was added to DNMT1.
Phenotypes for gene: DNMT1 were changed from Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121; Neuropathy, hereditary sensory, type IE, 614116 to Hereditary sensory neuropathy-deafness-dementia syndrome, MONDO:0013584
Publications for gene DNMT1 were changed from 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424 to 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424
Mendeliome v1.3356 DNM1L Chirag Patel Source Victorian Clinical Genetics Services was removed from DNM1L.
Source Literature was added to DNM1L.
Source ClinGen was added to DNM1L.
Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR); Optic atrophy 5 - MIM#610708 (AD) to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MONDO:0013726; Optic atrophy 5 - MIM#610708 (AD)
Publications for gene DNM1L were changed from 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748, 28969390, 30850373, 17460227 to 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748, 28969390, 30850373, 17460227
Mendeliome v1.3355 DES Chirag Patel Source Victorian Clinical Genetics Services was removed from DES.
Source ClinGen was added to DES.
Source Literature was added to DES.
Phenotypes for gene: DES were changed from Cardiomyopathy, dilated, 1I, MIM# 604765; Myopathy, myofibrillar, 1 , MIM#601419; Arrhythmogenic right ventricular cardiomyopathy to Cardiomyopathy, dilated, 1I, MIM# 604765; Myofibrillar myopathy 1, MONDO:0011076; Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
Publications for gene DES were changed from 10430757, 11728149, 17325244, 23300193, 31514951, 26724190, 23349452, 25557463, 19879535, 33947203, 19879535, 20423733, 23168288, 20829228, 22403400, 29212896, 22395865, 20718792 to 10430757, 11728149, 17325244, 23300193, 31514951, 26724190, 23349452, 25557463, 19879535, 33947203, 19879535, 20423733, 23168288, 20829228, 22403400, 29212896, 22395865, 20718792
Mendeliome v1.3354 DAAM2 Chirag Patel Publications for gene DAAM2 were changed from 33232676; 38860410; 36972684 to 33232676; 38860410; 36972684
Mendeliome v1.3353 FAP Sangavi Sivagnanasundram gene: FAP was added
gene: FAP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FAP were set to 40949908
Phenotypes for gene: FAP were set to congenital pulmonary airway malformation MONDO:0016580
Review for gene: FAP was set to RED
Added comment: Only 1 reported fetus with a diagnosis of congenital pulmonary airway malformation
Heterozygous variant identified - c.T269G:p.L90W.
The variant is present in gnomAD v4.1 - EAS AF - 0.007% (4 hets)
Sources: Literature
Mendeliome v1.3353 PDIA6 Sarah Milton edited their review of gene: PDIA6: Changed phenotypes: multiple congenital anomalies, MONDO:0019042, PDIA6-related
Mendeliome v1.3353 SF1 Sarah Milton changed review comment from: SF1 is involved in the first step of spliceosome complex assembly by recognizing the intron branchpoint consensus sequence at the 3′ splice site of the pre-mRNA. It is also involved in regulating alternative splicing

PMID: 40987292 describes 15 affected individuals with a neurodevelopmental disorder with monoallelic variants in SF1. Affected individuals had developmental delay, mild to moderate ID, behavioural disorders, seizures (3/15), brachydactyly (5/15), nail hypoplasia (5/15).
Variant types included missense and high impact LOF (nonsense and frameshift).

Most variants were appropriately rare in gnomAD v4 however one reported variant had 9 hets.
pLI for SF1 is 1 with overall few LOF variants in gene.

Supportive functional studies reported in publication. SF1 deficient neural progenitor cells showed altered gene expression in genes involved in neuronal differentiation/synaptic transmission and axonal guidance.
Sources: Literature; to: SF1 is involved in the first step of spliceosome complex assembly by recognizing the intron branchpoint consensus sequence at the 3′ splice site of the pre-mRNA. It is also involved in regulating alternative splicing

PMID: 40987292 describes 15 affected individuals with a neurodevelopmental disorder with monoallelic variants in SF1. Affected individuals had developmental delay, mild to moderate ID, behavioural disorders, seizures (3/15), brachydactyly (5/15), nail hypoplasia (5/15).
12 confirmed to have de novo variants including missense and high impact LOF (nonsense and frameshift).

Most variants were appropriately rare in gnomAD v4 however one reported variant had 9 hets.
pLI for SF1 is 1 with overall few LOF variants in gene.

Supportive functional studies reported in publication. SF1 deficient neural progenitor cells showed altered gene expression in genes involved in neuronal differentiation/synaptic transmission and axonal guidance.
Sources: Literature
Mendeliome v1.3353 SF1 Sarah Milton gene: SF1 was added
gene: SF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF1 were set to PMID: 40987292
Phenotypes for gene: SF1 were set to Neurodevelopmental disorder, MONDO:0700092, SF1-related
Review for gene: SF1 was set to GREEN
Added comment: SF1 is involved in the first step of spliceosome complex assembly by recognizing the intron branchpoint consensus sequence at the 3′ splice site of the pre-mRNA. It is also involved in regulating alternative splicing

PMID: 40987292 describes 15 affected individuals with a neurodevelopmental disorder with monoallelic variants in SF1. Affected individuals had developmental delay, mild to moderate ID, behavioural disorders, seizures (3/15), brachydactyly (5/15), nail hypoplasia (5/15).
Variant types included missense and high impact LOF (nonsense and frameshift).

Most variants were appropriately rare in gnomAD v4 however one reported variant had 9 hets.
pLI for SF1 is 1 with overall few LOF variants in gene.

Supportive functional studies reported in publication. SF1 deficient neural progenitor cells showed altered gene expression in genes involved in neuronal differentiation/synaptic transmission and axonal guidance.
Sources: Literature
Mendeliome v1.3353 DDR2 Chirag Patel Source Victorian Clinical Genetics Services was removed from DDR2.
Source Literature was added to DDR2.
Phenotypes for gene: DDR2 were changed from Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665; Warburg-Cinotti syndrome, MIM# 618175 to Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome, MONDO:0010077; Warburg-cinotti syndrome, MONDO:0032579
Publications for gene DDR2 were changed from 30449416, 19110212, 20223752, 24725993, 31406622, 33953858, 29884795, 35221872 to 30449416, 19110212, 20223752, 24725993, 31406622, 33953858, 29884795, 35221872
Mendeliome v1.3352 DEPDC5 Chirag Patel Source Victorian Clinical Genetics Services was removed from DEPDC5.
Source Literature was added to DEPDC5.
Publications for gene DEPDC5 were changed from 31444548; 23542697; 23542701; 36067010; 32848577 to 31444548; 23542697; 23542701; 36067010; 32848577
Mendeliome v1.3351 DHDDS Chirag Patel Source Victorian Clinical Genetics Services was removed from DHDDS.
Source Literature was added to DHDDS.
Publications for gene DHDDS were changed from 27343064, 21295283, 28130426, 29276052, 32483926, 36046393, 24078709, 28005406, 36046393, 29100083, 36628425, 34382076 to 27343064, 21295283, 28130426, 29276052, 32483926, 36046393, 24078709, 28005406, 36046393, 29100083, 36628425, 34382076
Mendeliome v1.3350 DHTKD1 Chirag Patel Classified gene: DHTKD1 as Green List (high evidence)
Mendeliome v1.3350 DHTKD1 Chirag Patel Gene: dhtkd1 has been classified as Green List (High Evidence).
Mendeliome v1.3349 DHTKD1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DHTKD1.
Source Victorian Clinical Genetics Services was removed from DHTKD1.
Source ClinGen was added to DHTKD1.
Phenotypes for gene: DHTKD1 were changed from Alpha-aminoadipic and alpha-ketoadipic aciduria MIM#204750, AR; Charcot-Marie-Tooth disease, axonal, type 2Q, MIM#615025 to 2-aminoadipic 2-oxoadipic aciduria MONDO:0008774; Charcot-Marie-Tooth disease axonal type 2Q MONDO:0014012
Publications for gene DHTKD1 were changed from 26141459, 25860818, 23141293, 23141294, 29661920, 28902413 to 26141459, 25860818, 23141293, 23141294, 29661920, 28902413
Rating Changed from Green List (high evidence) to Red List (low evidence)
Mendeliome v1.3348 DHX37 Chirag Patel Phenotypes for gene: DHX37 were changed from 46,XY gonadal dysgenesis; testicular regression syndrome (TRS); Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731 to 46,XY sex reversal 11, MONDO:8000015; Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731
Publications for gene DHX37 were changed from 31337883; 31745530; 31287541; 26539891; 31256877 to 31337883; 31745530; 31287541; 26539891; 31256877
Mendeliome v1.3347 DIAPH1 Chirag Patel Publications for gene DIAPH1 were changed from 27808407; 28003573; 28815995; 26912466; 24781755; 26463574; 33662367; 36212620; 39076976; 39120629 to 27808407; 28003573; 28815995; 26912466; 24781755; 26463574; 33662367; 36212620; 39076976; 39120629
Mendeliome v1.3346 ZSWIM7 Sangavi Sivagnanasundram changed review comment from: Established gene-disease association. Reported in unrelated individuals with either azoospermia or primary ovarian insufficiency

Spermatogenic failure:

PMID: 32719396
Homozygous males presenting with non-obstructive azoospermia
c.201+1G>T - absent from gnomAD v4.1
c.231_232del;p.(Cys78Phefs*21) - FAF 0.04%

PMID: 33713115 - 2 unrelated Chinese males with non-obstructive azoospermia from consanguineous families presented with homozygous c.231_232del;p.(Cys78Phefs*21)
CRISPR/Cas9 mouse model showed that in the mutant mice had smaller testes compared to their control littermates and no sperm in histological analysis recapitulating spermatogenic arrest.

Primary ovarian insufficiency (POI):

PMID: 40991243
Four french individuals with a diagnosis of premature ovarian insufficiency (POI) identified with variants in ZSWIM7

Patient 1: Homozygous deletion c.231_232del
Patient 2: Compound het c.231_232del;c.22del (p.Val8LeufsTer6)
Patient 3: Compound het c.231_232del; c.151C>T (NFE AF 0.002%)
Paitent 4: Homozygous c.176C>T p.(Arg51Ter)

PMID: 40991243
Two sisters from a consanguineous pedigree presented in adolescence with absent puberty and primary amenorrhea
Both sisters homozygous for c.173G>C and unaffected mother heterozygous for the variant
Sources: Literature; to: Established gene-disease association. Biallelic variants reported in unrelated individuals with either azoospermia or primary ovarian insufficiency

Spermatogenic failure:

PMID: 32719396
Homozygous males presenting with non-obstructive azoospermia
c.201+1G>T - absent from gnomAD v4.1
c.231_232del;p.(Cys78Phefs*21) - FAF 0.04%

PMID: 33713115 - 2 unrelated Chinese males with non-obstructive azoospermia from consanguineous families presented with homozygous c.231_232del;p.(Cys78Phefs*21)
CRISPR/Cas9 mouse model showed that in the mutant mice had smaller testes compared to their control littermates and no sperm in histological analysis recapitulating spermatogenic arrest.

Primary ovarian insufficiency (POI):

PMID: 40991243
Four french individuals with a diagnosis of premature ovarian insufficiency (POI) identified with variants in ZSWIM7

Patient 1: Homozygous deletion c.231_232del
Patient 2: Compound het c.231_232del;c.22del (p.Val8LeufsTer6)
Patient 3: Compound het c.231_232del; c.151C>T (NFE AF 0.002%)
Paitent 4: Homozygous c.176C>T p.(Arg51Ter)

PMID: 40991243
Two sisters from a consanguineous pedigree presented in adolescence with absent puberty and primary amenorrhea
Both sisters homozygous for c.173G>C and unaffected mother heterozygous for the variant
Sources: Literature
Mendeliome v1.3346 ZSWIM7 Sangavi Sivagnanasundram gene: ZSWIM7 was added
gene: ZSWIM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZSWIM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSWIM7 were set to 32719396, 33713115, 40991243, 40991243
Phenotypes for gene: ZSWIM7 were set to Spermatogenic failure 71 MONDO:0030787; Ovarian dysgenesis 10 MONDO:0030736
Review for gene: ZSWIM7 was set to GREEN
Added comment: Established gene-disease association. Reported in unrelated individuals with either azoospermia or primary ovarian insufficiency

Spermatogenic failure:

PMID: 32719396
Homozygous males presenting with non-obstructive azoospermia
c.201+1G>T - absent from gnomAD v4.1
c.231_232del;p.(Cys78Phefs*21) - FAF 0.04%

PMID: 33713115 - 2 unrelated Chinese males with non-obstructive azoospermia from consanguineous families presented with homozygous c.231_232del;p.(Cys78Phefs*21)
CRISPR/Cas9 mouse model showed that in the mutant mice had smaller testes compared to their control littermates and no sperm in histological analysis recapitulating spermatogenic arrest.

Primary ovarian insufficiency (POI):

PMID: 40991243
Four french individuals with a diagnosis of premature ovarian insufficiency (POI) identified with variants in ZSWIM7

Patient 1: Homozygous deletion c.231_232del
Patient 2: Compound het c.231_232del;c.22del (p.Val8LeufsTer6)
Patient 3: Compound het c.231_232del; c.151C>T (NFE AF 0.002%)
Paitent 4: Homozygous c.176C>T p.(Arg51Ter)

PMID: 40991243
Two sisters from a consanguineous pedigree presented in adolescence with absent puberty and primary amenorrhea
Both sisters homozygous for c.173G>C and unaffected mother heterozygous for the variant
Sources: Literature
Mendeliome v1.3346 DIAPH1 Chirag Patel Publications for gene DIAPH1 were changed from 27808407; 28003573; 28815995; 26912466; 24781755; 26463574 to 27808407; 28003573; 28815995; 26912466; 24781755; 26463574
Mendeliome v1.3345 DIAPH1 Chirag Patel Publications for gene DIAPH1 were changed from 27808407; 28003573; 28815995; 26463574; 26912466; 24781755 to 27808407; 28003573; 28815995; 26463574; 26912466; 24781755
Mendeliome v1.3344 DIAPH1 Chirag Patel Publications for gene DIAPH1 were changed from 27808407; 28003573; 28815995; 26463574; 24781755 to 27808407; 28003573; 28815995; 26463574; 24781755
Mendeliome v1.3343 DIAPH1 Chirag Patel Phenotypes for gene: DIAPH1 were changed from DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome, MONDO:0044635 to DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome, MONDO:0044635; Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, MONDO:0014714
Publications for gene DIAPH1 were changed from 24781755; 24781755; 27808407; 28003573; 28815995; 26463574 to 24781755; 24781755; 27808407; 28003573; 28815995; 26463574
Mendeliome v1.3342 DIAPH1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DIAPH1.
Source Literature was added to DIAPH1.
Phenotypes for gene: DIAPH1 were changed from Deafness; thrombocytopenia 124900; Seizures; cortical blindness; microcephaly 616632 to DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome, MONDO:0044635
Mendeliome v1.3341 PDIA6 Sarah Milton reviewed gene: PDIA6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40974269, 35856135, 33495992; Phenotypes: Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes and polycystic kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3341 DLX3 Chirag Patel reviewed gene: DLX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15666299, 9467018, 18203197, 9783705, 10466415, 9467018; Phenotypes: Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism, MONDO:0007093, Tricho-dento-osseous syndrome, MONDO:0008592; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3341 DLX3 Chirag Patel Phenotypes for gene: DLX3 were changed from Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism, MONDO:0007093 to Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism, MONDO:0007093; Tricho-dento-osseous syndrome, MONDO:0008592
Publications for gene DLX3 were changed from 15666299, 9467018, 18203197, 9783705, 10466415, 9467018 to 15666299, 9467018, 18203197, 9783705, 10466415, 9467018
Mendeliome v1.3340 DLX3 Chirag Patel Classified gene: DLX3 as Green List (high evidence)
Mendeliome v1.3340 DLX3 Chirag Patel Gene: dlx3 has been classified as Green List (High Evidence).
Mendeliome v1.3339 DLX3 Chirag Patel Source Victorian Clinical Genetics Services was removed from DLX3.
Source Literature was added to DLX3.
Phenotypes for gene: DLX3 were changed from Amelogenesis imperfecta, type IV, MIM# 104510; Trichodontoosseous syndrome, MIM# 190320 to Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism, MONDO:0007093
Publications for gene DLX3 were changed from 9467018; 15666299 to 9467018; 15666299
Rating Changed from Green List (high evidence) to Red List (low evidence)
Mendeliome v1.3338 RNF31 Zornitza Stark Marked gene: RNF31 as ready
Mendeliome v1.3338 RNF31 Zornitza Stark Added comment: Comment when marking as ready: Alias: HOIP
Mendeliome v1.3338 RNF31 Zornitza Stark Gene: rnf31 has been classified as Green List (High Evidence).
Mendeliome v1.3338 LEO1 Chirag Patel Classified gene: LEO1 as Green List (high evidence)
Mendeliome v1.3338 LEO1 Chirag Patel Gene: leo1 has been classified as Green List (High Evidence).
Mendeliome v1.3337 LEO1 Chirag Patel reviewed gene: LEO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40993282, 33004838, 31785789, 40671880, 29674594; Phenotypes: Neurodevelopmental disorder MONDO:0700092, LEO-1 related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3337 MDC1 Zornitza Stark Marked gene: MDC1 as ready
Mendeliome v1.3337 MDC1 Zornitza Stark Gene: mdc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3337 MDC1 Zornitza Stark Publications for gene: MDC1 were set to PMID: 40954969, 34089056
Mendeliome v1.3336 MDC1 Zornitza Stark Classified gene: MDC1 as Amber List (moderate evidence)
Mendeliome v1.3336 MDC1 Zornitza Stark Gene: mdc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3335 SYNE2 Zornitza Stark Phenotypes for gene: SYNE2 were changed from Emery-Dreifuss muscular dystrophy 5, autosomal dominant MIM#612999 to Emery-Dreifuss muscular dystrophy 5, autosomal dominant MIM#612999; Neurodevelopmental disorder, MONDO:0700092, SYNE2 related
Mendeliome v1.3334 SYNE2 Zornitza Stark Publications for gene: SYNE2 were set to 32184094; 17761684; 40757551
Mendeliome v1.3333 SYNE2 Zornitza Stark Mode of inheritance for gene: SYNE2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3332 KLK15 Sangavi Sivagnanasundram gene: KLK15 was added
gene: KLK15 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: KLK15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLK15 were set to 40949095
Phenotypes for gene: KLK15 were set to hypermobile Ehlers-Danlos syndrome MONDO:0007523
Review for gene: KLK15 was set to AMBER
Added comment: Two unrelated families with individuals affected with hEDS
Heterozygous p.Gly226Asp was identified in both families and segregated with disease across other affected individuals and not presented in unaffected family members.
Note: p.Gly226Asp - FAF 0.4970% in gnomAD v4.1

CRISPR-Cas9-generated Klk15G224D/+ knock in mouse model showed a decrease in tendon elasicity, mitral valve prolapse, collagen fibril thinning which is supportive to show the mouse model recapitulated human phenotype.

More evidence is required to support gene-disease association given only one variant in two families and supportive mouse model have been reported.
Sources: Other
Mendeliome v1.3332 CNTD2 Zornitza Stark Marked gene: CNTD2 as ready
Mendeliome v1.3332 CNTD2 Zornitza Stark Gene: cntd2 has been classified as Green List (High Evidence).
Mendeliome v1.3332 CNTD2 Zornitza Stark Classified gene: CNTD2 as Green List (high evidence)
Mendeliome v1.3332 CNTD2 Zornitza Stark Gene: cntd2 has been classified as Green List (High Evidence).
Mendeliome v1.3331 CNTD2 Zornitza Stark Tag new gene name tag was added to gene: CNTD2.
Mendeliome v1.3331 CLIC5 Chirag Patel Classified gene: CLIC5 as Green List (high evidence)
Mendeliome v1.3331 CLIC5 Chirag Patel Gene: clic5 has been classified as Green List (High Evidence).
Mendeliome v1.3330 CLIC5 Chirag Patel reviewed gene: CLIC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 40957967, 40928595, 33114113; Phenotypes: Autosomal recessive nonsyndromic hearing loss 103, MONDO:0014469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3330 CLIC5 Chirag Patel Source Victorian Clinical Genetics Services was removed from CLIC5.
Source Literature was added to CLIC5.
Phenotypes for gene: CLIC5 were changed from Deafness, autosomal recessive 103, MIM# 616042 to Autosomal recessive nonsyndromic hearing loss 103, MONDO:0014469
Mendeliome v1.3329 CNTD2 Sangavi Sivagnanasundram gene: CNTD2 was added
gene: CNTD2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: CNTD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTD2 were set to 41005306
Phenotypes for gene: CNTD2 were set to Oocyte/zygote/embryo maturation arrest MONDO:0014769
Review for gene: CNTD2 was set to GREEN
Added comment: HGNC approved new gene name: CCNP

3 unrelated women presenting with primary infertility and oocyte/embryo defects in IVF.
Different biallelic variants were identified - all variants were either absent or rare enough in gnomAD v4.1 for AR gene (p.L59Wfs*11, p.Y231N, and c.358-1G>A).

In vivo mouse model showed that the overexpression of mutant CNTD2 mRNA in mouse zygotes led to early embryonic arrest.
Sources: Other
Mendeliome v1.3329 SYNE2 Chirag Patel reviewed gene: SYNE2: Rating: RED; Mode of pathogenicity: None; Publications: 34573277; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, SYNE2 related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3329 INTS6 Zornitza Stark Phenotypes for gene: INTS6 were changed from to Neurodevelopmental disorder, MONDO:0700092, INTS6-related
Mendeliome v1.3328 INTS6 Zornitza Stark Mode of inheritance for gene: INTS6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3327 INTS6 Zornitza Stark Classified gene: INTS6 as Green List (high evidence)
Mendeliome v1.3327 INTS6 Zornitza Stark Gene: ints6 has been classified as Green List (High Evidence).
Mendeliome v1.3326 CCDC188 Zornitza Stark Marked gene: CCDC188 as ready
Mendeliome v1.3326 CCDC188 Zornitza Stark Gene: ccdc188 has been classified as Green List (High Evidence).
Mendeliome v1.3326 CCDC188 Zornitza Stark Classified gene: CCDC188 as Green List (high evidence)
Mendeliome v1.3326 CCDC188 Zornitza Stark Gene: ccdc188 has been classified as Green List (High Evidence).
Mendeliome v1.3325 SPDYC Zornitza Stark Marked gene: SPDYC as ready
Mendeliome v1.3325 SPDYC Zornitza Stark Gene: spdyc has been classified as Green List (High Evidence).
Mendeliome v1.3325 PCDHA13 Zornitza Stark Marked gene: PCDHA13 as ready
Mendeliome v1.3325 PCDHA13 Zornitza Stark Gene: pcdha13 has been classified as Red List (Low Evidence).
Mendeliome v1.3325 PCDHA13 Chirag Patel gene: PCDHA13 was added
gene: PCDHA13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCDHA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCDHA13 were set to 40988636
Phenotypes for gene: PCDHA13 were set to Hypoplastic left heart syndrome, MONDO:0004933
Review for gene: PCDHA13 was set to RED
Added comment: WES in 68 subjects with HLHS identified 1 individual with co-occurrence (i.e. digenic) of a SAP130 gene variant (p. S639G) and PCDHA13 gene variant (p. A22V). GnomAD frequencies for variants are: 0.00003% (PCDHA13 variant) and 0.01% with numerous homozygotes (SAP130 variant). The PCDHA13 variant is situated in a region highly conserved across the PCDHA gene family (which is highly homologous), especially PCDHA10 which is the ortholog of mouse Pcdha9.

Mouse and zebrafish modeling showed that Sap130 mediates left ventricular hypoplasia, and Pcdha9 increases penetrance of aortic valve abnormalities. Mutations in Sap130 and Pcdha9 were validated by CRISPR–Cas9 genome editing in mice as being digenic causes of HLHS.
Sources: Literature
Mendeliome v1.3324 SPDYC Chirag Patel Classified gene: SPDYC as Green List (high evidence)
Mendeliome v1.3324 SPDYC Chirag Patel Gene: spdyc has been classified as Green List (High Evidence).
Mendeliome v1.3323 SPDYC Chirag Patel gene: SPDYC was added
gene: SPDYC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPDYC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPDYC were set to 41005306
Phenotypes for gene: SPDYC were set to Primary ovarian failure, MONDO:0005387
Review for gene: SPDYC was set to GREEN
Added comment: 4 unrelated female patients with primary infertility caused by oocyte/embryo defects, from a large cohort of 3,627 patients. WES identified rare biallelic variants in SPDYC gene (p.R52Vfs∗50, p.R188C, p.P287H). Overexpression of mutant SPDYC mRNA in mouse oocytes caused disruption of the ability of the protein to overcome milrinone-mediated inhibition of meiotic resumption with two of the variants (p.R52Vfs∗50 and p.R188C). SPDYC is involved in crucial processes involving cyclin-dependent kinases during the phase transition of the mitotic cell cycle.
Sources: Literature
Mendeliome v1.3322 CCDC188 Chirag Patel gene: CCDC188 was added
gene: CCDC188 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC188 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC188 were set to 41004021
Phenotypes for gene: CCDC188 were set to Male infertility due to acephalic spermatozoa, MONDO:0035153
Review for gene: CCDC188 was set to GREEN
Added comment: 2 patients from 2 unrelated families with acephalic spermatozoa syndrome. WES identified biallelic variants in CCDC188 gene (1 x homozygous, 1 x compound heterozygous). The variants (c.481C > T [p.Gln161*] and c.1022 + 1G > A [p. K325Afs*110]) were rare in gnomAD and segregated in the family with heterozygous carrier parents. Western blotting, RT-PCR, qPCR, and immunofluorescence showed depletion of CCDC188 protein (and SUN5 and PMFBP1 protein) in patient sperm. Mutations in SUN5 and PMFBP1 genes account for 75% patients with acephalic spermatozoa syndrome.
Sources: Literature
Mendeliome v1.3322 CCDC188 Chirag Patel gene: CCDC188 was added
gene: CCDC188 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC188 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC188 were set to 41004021
Phenotypes for gene: CCDC188 were set to Male infertility due to acephalic spermatozoa, MONDO:0035153
Review for gene: CCDC188 was set to GREEN
Added comment: 2 patients from 2 unrelated families with acephalic spermatozoa syndrome. WES identified biallelic variants in CCDC188 gene (1 x homozygous, 1 x compound heterozygous). The variants (c.481C > T [p.Gln161*] and c.1022 + 1G > A [p. K325Afs*110]) were rare in gnomAD and segregated in the family with heterozygous carrier parents. Western blotting, RT-PCR, qPCR, and immunofluorescence showed depletion of CCDC188 protein (and SUN5 and PMFBP1 protein) in patient sperm. Mutations in SUN5 and PMFBP1 genes account for 75% patients with acephalic spermatozoa syndrome.
Sources: Literature
Mendeliome v1.3321 INTS6 Sarah Milton changed review comment from: INTS6 encodes a member of the integrator complex which plays a role in RNA polymerase II transcription termination and small nuclear RNA processing.

PMID: 40966122 describes 24 affected individuals from 23 families with a variable neurodevelopmental disorder. Variant types included monoallelic missense, nonsense, frameshift and splice site.
Phenotypes included autism, variable language and motor delay, variable ID/developmental delay, sleep disturbances and epilepsy in a small subset.

21 variants were confirmed to be de novo.
All variants either absent in gnomad v4 or had 1 heterozygote only.
pLI for INTS6 is 1 and few overall LOF variants in gnomAD v4 in gene.

Supportive functional studies including biallelic knockout mice demonstrating abnormal brain morphology. Heterozygous knockout mice assessed to have abnormal behaviour and reduced learning efficiency and memory retention. Some variant specific studies performed consistent with loss of function mechanism.; to: INTS6 encodes a member of the integrator complex which plays a role in RNA polymerase II transcription termination and small nuclear RNA processing.

PMID: 40966122 describes 24 affected individuals from 23 families with a neurodevelopmental disorder. Variant types included monoallelic missense, nonsense, frameshift and splice site.
Phenotypes included autism, variable language and motor delay, variable ID/developmental delay, sleep disturbances and epilepsy in a small subset.

21 variants were confirmed to be de novo.
All variants either absent in gnomad v4 or had 1 heterozygote only.
pLI for INTS6 is 1 and few overall LOF variants in gnomAD v4 in gene.

Supportive functional studies including biallelic knockout mice demonstrating abnormal brain morphology. Heterozygous knockout mice assessed to have abnormal behaviour and reduced learning efficiency and memory retention. Some variant specific studies performed consistent with loss of function mechanism.
Mendeliome v1.3321 INTS6 Sarah Milton reviewed gene: INTS6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40966122; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, INTS6-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3321 TH Zornitza Stark Marked gene: TH as ready
Mendeliome v1.3321 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Mendeliome v1.3321 TH Zornitza Stark Classified gene: TH as Green List (high evidence)
Mendeliome v1.3321 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Mendeliome v1.3320 TH Zornitza Stark changed review comment from: Well established association with infantile onset DOPA-reponsive dystonia.
Sources: Literature; to: Well established association with infantile onset DOPA-responsive dystonia.
Sources: Literature
Mendeliome v1.3320 TH Zornitza Stark gene: TH was added
gene: TH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TH were set to Segawa syndrome, recessive MIM#605407
Review for gene: TH was set to GREEN
Added comment: Well established association with infantile onset DOPA-reponsive dystonia.
Sources: Literature
Mendeliome v1.3319 TCIRG1 Zornitza Stark Phenotypes for gene: TCIRG1 were changed from Osteopetrosis, autosomal recessive 1, MIM# 259700 to Osteopetrosis, autosomal recessive 1, MIM# 259700; severe congenital neutropenia, MONDO:0018542, TCIRG1-related
Mendeliome v1.3318 TCIRG1 Zornitza Stark Publications for gene: TCIRG1 were set to 34624559; 34210262; 30084437; 28816234
Mendeliome v1.3317 TCIRG1 Zornitza Stark Mode of inheritance for gene: TCIRG1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3316 TCIRG1 Zornitza Stark edited their review of gene: TCIRG1: Added comment: PMID: 40964614, now total of 6 families with neutropenia and supportive functional data, upgrade mono-allelic association to Green.; Changed publications: 34624559, 34210262, 30084437, 28816234, 40964614
Mendeliome v1.3316 MDC1 Sarah Milton gene: MDC1 was added
gene: MDC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDC1 were set to PMID: 40954969, 34089056
Phenotypes for gene: MDC1 were set to Oligoasthenoteratozoospermia, MONDO:0850098, MDC1-related
Review for gene: MDC1 was set to AMBER
Added comment: MDC1 encodes mediator of DNA damage checkpoint I protein.

PMID: 40954969 describes 2 affected individuals with biallelic loss of function (nonsense and start loss) variants in MDC1 with reduced sperm count, abnormal morphology and poor motility. 1 family consanguineous.
PMID: 34089056 describes 1 similarly affected individual with 2 loss of function variants not confirmed in trans.
All adequately rare in gnomad v4.
No homozygous NMD predicted variants in gnomad v4.

Knockout mice models show meiotic arrest in spermatocytes which subsequently undergo apoptosis.

Functional studies performed in PMID:40954969 showed lack of protein in affected patient cells and lack of colocalization usual partner protein. Didn't demonstrate conclusively loss of downstream function.
Sources: Literature
Mendeliome v1.3316 SPAST Zornitza Stark Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant (MIM#182601), AD to Spastic paraplegia 4, autosomal dominant (MIM#182601), AD; Cerebral Palsy MONDO:0006497, SPAST-related, AR
Mendeliome v1.3315 SPAST Zornitza Stark Publications for gene: SPAST were set to 30476002; 30006150
Mendeliome v1.3314 SPAST Zornitza Stark Mode of inheritance for gene: SPAST was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3313 SPAST Zornitza Stark reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: None; Publications: 41000004; Phenotypes: Cerebral Palsy MONDO:0006497, SPAST-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3313 RNU2-2P Zornitza Stark Publications for gene: RNU2-2P were set to 40210679; 40442284
Mendeliome v1.3312 RNU2-2P Zornitza Stark Mode of inheritance for gene: RNU2-2P was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3311 RNU2-2P Zornitza Stark changed review comment from: PMID 40950445: reports bi-alleic cases in a cohort of over 100 individuals. One variant frequently de novo in trans with inherited variant.; to: PMID 40950445: reports bi-allelic cases in a cohort of over 100 individuals. One variant frequently de novo in trans with inherited variant.
Mendeliome v1.3311 RNU2-2P Zornitza Stark changed review comment from: PMID 40950445: reports bi-alleic cases. One variant frequently de novo in trans with inherited variant.; to: PMID 40950445: reports bi-alleic cases in a cohort of over 100 individuals. One variant frequently de novo in trans with inherited variant.
Mendeliome v1.3311 RNU2-2P Zornitza Stark edited their review of gene: RNU2-2P: Added comment: PMID 40950445: reports bi-alleic cases. One variant frequently de novo in trans with inherited variant.; Changed publications: 40210679, 40442284, 40950445; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3311 PKD1 Zornitza Stark Mode of inheritance for gene: PKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3310 PKD1 Zornitza Stark edited their review of gene: PKD1: Added comment: Rare reports of bi-allelic disease presenting antenatally.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3310 OSMR Zornitza Stark Phenotypes for gene: OSMR were changed from Amyloidosis, primary localized cutaneous, 1 - MIM#105250 to Amyloidosis, primary localized cutaneous, 1 - MIM#105250; Inborn error of immunity, MONDO:0003778, OSMR-related
Mendeliome v1.3309 OSMR Zornitza Stark Publications for gene: OSMR were set to 19375894; 19528426; 25054142; 20507362; 19690585
Mendeliome v1.3308 OSMR Zornitza Stark Mode of inheritance for gene: OSMR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3307 OSMR Zornitza Stark reviewed gene: OSMR: Rating: GREEN; Mode of pathogenicity: None; Publications: 40970115; Phenotypes: Inborn error of immunity, MONDO:0003778, OSMR-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3307 MAP3K1 Zornitza Stark Publications for gene: MAP3K1 were set to 21129722; 32986312
Mendeliome v1.3306 MAP3K1 Zornitza Stark commented on gene: MAP3K1: PMID 39062623: single family reported with deafness and homozygous missense, but two supportive mouse models. RED for this association and MOI.
Mendeliome v1.3306 ASXL3 Zornitza Stark Publications for gene: ASXL3 were set to 28100473; 27901041; 23383720
Mendeliome v1.3305 ASXL3 Zornitza Stark changed review comment from: PMID 32696347: two families with compound het variants and congenital heart disease, some functional data.; to: PMID 32696347: two families with compound het variants and congenital heart disease, some functional data. RED for this MOI and association.
Mendeliome v1.3305 ASXL3 Zornitza Stark edited their review of gene: ASXL3: Added comment: PMID 32696347: two families with compound het variants and congenital heart disease, some functional data.; Changed publications: 28100473, 27901041, 23383720, 32696347
Mendeliome v1.3305 MSTO1 Lucy Spencer reviewed gene: MSTO1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3305 EMB Zornitza Stark Marked gene: EMB as ready
Mendeliome v1.3305 EMB Zornitza Stark Gene: emb has been classified as Red List (Low Evidence).
Mendeliome v1.3305 MRPS36 Zornitza Stark Marked gene: MRPS36 as ready
Mendeliome v1.3305 MRPS36 Zornitza Stark Gene: mrps36 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3305 MRPS36 Zornitza Stark Tag new gene name tag was added to gene: MRPS36.
Mendeliome v1.3305 MRC2 Krithika Murali Marked gene: MRC2 as ready
Mendeliome v1.3305 MRC2 Krithika Murali Gene: mrc2 has been classified as Red List (Low Evidence).
Mendeliome v1.3305 MRC2 Krithika Murali gene: MRC2 was added
gene: MRC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MRC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRC2 were set to PMID: 38953222
Phenotypes for gene: MRC2 were set to Wolff-Parkinson-White syndrome - MONDO:0008685, MRC2-related
Review for gene: MRC2 was set to RED
Added comment: PMID: 38953222 - Multiple indiviuals from 1 family with het MRC2 variant c.2969A>G; p.Glu990Gly and SVT or WPW reported. In vivo electrophysiological studies/optical mapping in knock-in mice with the E990G variant demonstrated higher incidence of inducible SVT and retrograde conduction through an accessory pathway. Studies in human cardiac fibroblasts revealed enhanced migration in Mrc2-knockdown cells.
Sources: Literature
Mendeliome v1.3304 EMB Krithika Murali gene: EMB was added
gene: EMB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMB were set to PMID: 40999499
Phenotypes for gene: EMB were set to Hirschsprung disease - MONDO:0018309, EMB-related
Added comment: Li et al 2025 report enrichment of rare EMB variants in a cohort of patients with Hirschsprung disease. No additional phenotypic or variant information provided. Various in vitro studies and zebrafish/knockout mouse model associate loss of EMB with HSCR phenotype.
Sources: Literature
Mendeliome v1.3303 MRPS36 Krithika Murali Classified gene: MRPS36 as Amber List (moderate evidence)
Mendeliome v1.3303 MRPS36 Krithika Murali Gene: mrps36 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3302 MRPS36 Krithika Murali gene: MRPS36 was added
gene: MRPS36 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MRPS36 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS36 were set to PMID: 41018056; 38685873
Phenotypes for gene: MRPS36 were set to Leigh syndrome - MONDO:0009723, MRPS36/KGD4-related
Review for gene: MRPS36 was set to AMBER
Added comment: 3 individuals from 2 unrelated families reported with biallelic MRPS36 variants (current HGNC is KGD4). Gene encodes E4 subunit of OGDHC complex. Individuals present with a phenotype consistent with Leigh syndrome including seizures, hypotonia, dystonia, brain imaging anomalies, persistent lactic acidosis. Cardiomyopathy also reported.

Patient-derived fibroblast studies demonstrates reduced OGDHC enzymatic activity, however, this functional evidence is not gene or variant-specific.
Sources: Literature
Mendeliome v1.3301 CPD Sarah Milton changed review comment from: CPD encodes carboxypeptidase D which is part of the metallocarboxylpeptidases family. These enzymes are zinc dependent and cleave c terminal arginine and lysine. Which in turn has a role in production of nitric oxide which is known to play role in the cochlea.

PMID: 41026541 describes 5 individuals from 3 families with biallelic missense variants in CPD who have prelingual onset bilateral profound SNHL. No syndromic features were noted in affected probands.
All variants appropriately rare in gnomad v4 for a rare recessive disorder.
No homozygous loss of function variants in gene in gnomad v4.
All families consanguineous.

Functional studies demonstrated reduction in nitric oxide levels in patient cells as well as increased apoptosis with rescue upon introduction on L arginine. Proposed mechanism of disease is loss of function.
Drosophila studies demonstrated disrupted Johnston’s organ morphology and impaired auditory transduction with partial rescue by arginine. Other supportive functional models discussed in paper.

Authors suggest potential treatment of affected individuals with arginine supplementation.
Sources: Literature; to: CPD encodes carboxypeptidase D which is part of the metallocarboxylpeptidases family. These enzymes are zinc dependent and cleave c terminal arginine and lysine. Which in turn has a role in production of nitric oxide which is known to assist in function of the cochlea.

PMID: 41026541 describes 5 individuals from 3 families with biallelic missense variants in CPD who have prelingual onset bilateral profound SNHL. No syndromic features were noted in affected probands.
All variants appropriately rare in gnomad v4 for a rare recessive disorder.
No homozygous loss of function variants in gene in gnomad v4.
All families consanguineous.

Functional studies demonstrated reduction in nitric oxide levels in patient cells as well as increased apoptosis with rescue upon introduction on L arginine. Proposed mechanism of disease is loss of function.
Drosophila studies demonstrated disrupted Johnston’s organ morphology and impaired auditory transduction with partial rescue by arginine. Other supportive functional models discussed in paper.

Authors suggest potential treatment of affected individuals with arginine supplementation.
Sources: Literature
Mendeliome v1.3301 JPH2 Zornitza Stark Classified gene: JPH2 as Green List (high evidence)
Mendeliome v1.3301 JPH2 Zornitza Stark Gene: jph2 has been classified as Green List (High Evidence).
Mendeliome v1.3300 CPD Zornitza Stark Marked gene: CPD as ready
Mendeliome v1.3300 CPD Zornitza Stark Gene: cpd has been classified as Green List (High Evidence).
Mendeliome v1.3300 CPD Zornitza Stark Classified gene: CPD as Green List (high evidence)
Mendeliome v1.3300 CPD Zornitza Stark Gene: cpd has been classified as Green List (High Evidence).
Mendeliome v1.3299 THAP4 Zornitza Stark Marked gene: THAP4 as ready
Mendeliome v1.3299 THAP4 Zornitza Stark Gene: thap4 has been classified as Red List (Low Evidence).
Mendeliome v1.3299 THAP4 Zornitza Stark gene: THAP4 was added
gene: THAP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: THAP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THAP4 were set to 40949908
Phenotypes for gene: THAP4 were set to Congenital pulmonary airway malformation, MONDO:0016580, THAP4-related
Review for gene: THAP4 was set to RED
Added comment: Single individual with a missense variant reported in a CPAM cohort.
Sources: Literature
Mendeliome v1.3298 ALDH1B1 Zornitza Stark Marked gene: ALDH1B1 as ready
Mendeliome v1.3298 ALDH1B1 Zornitza Stark Gene: aldh1b1 has been classified as Red List (Low Evidence).
Mendeliome v1.3298 ALDH1B1 Zornitza Stark gene: ALDH1B1 was added
gene: ALDH1B1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALDH1B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALDH1B1 were set to 40988636
Phenotypes for gene: ALDH1B1 were set to Congenital pulmonary airway malformation, MONDO:0016580, ALDH1B1-related
Review for gene: ALDH1B1 was set to RED
Added comment: Single individual with missense variant reported in a CPAM cohort.
Sources: Literature
Mendeliome v1.3297 MUC3A Zornitza Stark Marked gene: MUC3A as ready
Mendeliome v1.3297 MUC3A Zornitza Stark Gene: muc3a has been classified as Red List (Low Evidence).
Mendeliome v1.3297 MUC3A Zornitza Stark gene: MUC3A was added
gene: MUC3A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MUC3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MUC3A were set to 40949908
Phenotypes for gene: MUC3A were set to Congenital pulmonary airway malformation, MONDO:0016580, MUC3A-related
Review for gene: MUC3A was set to RED
Added comment: Three individuals with LoF variants identified in a CPAM cohort. However, all three variants are present in gnomAD, one of them in over 1500 individuals.
Sources: Literature
Mendeliome v1.3296 GTF2I Zornitza Stark Marked gene: GTF2I as ready
Mendeliome v1.3296 GTF2I Zornitza Stark Gene: gtf2i has been classified as Green List (High Evidence).
Mendeliome v1.3296 DMRT2 Krithika Murali edited their review of gene: DMRT2: Added comment: PMID: 29681102 Bouman et al 2018 paper SH3PXD2B reviewed - not coding in canonical transcript, 4 homs in gnomAD v4. In summary, 2 unrelated individuals with severe skeletal dysplasia and other extra-skeletal features and one mouse model with severe skeletal dysplasia supporting Green classification.; Changed rating: GREEN
Mendeliome v1.3296 DMRT2 Krithika Murali changed review comment from: PMID: 41014130 Rips et al 2025 report a newborn of consanguineous non-AJ ancestry with severe costovertebral malformations, dysmorphism and homozygous LoF DMRT2 variant identified on singleton exome sequencing (no parental testing). The patient also had congenital heart disease, bilateral duplicated kidneys, cleft palate, inguinal hernias.This patient also had immunodeficiency with thymic aplasia, absence of TRECs on NBS, profound lymphopenia with death at 3 months of age from CMV pneumonitis. Prenatal features include severe polyhydramnios.

PMID: 29681102 Bouman et al 2018 report a male neonate of consanguineous North African descent with thoracic vertebral anomalies, rib anomalies, dysmorphism and severe respiratory deficiency resulting in neonatal death at 9 days of age. Extra-skeletal anomalies included aberrate right subclavian artery, non-functional left kidney and tetehterd cord.Prenatal features included increased NT (8.0mm), scoliosis (15+4 weeks), IUGR/kyphoscoliosis/small thoracic cage (28+2 weeks). Trio WES identified a homozygous start-loss DMRT2 variant (c.1A>T p.Met1?) classified as a VUS. In addition, a homozygous canonical acceptor site variant in the non-canonical transcript was detected in SH3PXD2B associated with Frank-Ter Haar syndrome which is also known to have skeletal features including rarely respiratory failure leading to neonatal death (PMID: 31978614). The parents were heterozygous for both sets of variants and the unaffected sibling was homozygous wild-type.

PMID: 16387892 Seo et al 2006 report a knockout mouse model with abnormal rib and sternal development, respiratory insufficiency.

Overlapping features between the 2 unrelated patients and the mouse model include severe skeletal manifestations. However, one of the reported cases also had an alternative genomic finding relevant to skeletal issues. Other overlapping features observed in the 2 patients and not in the mouse include congenital heart defects and CAKUT.
Sources: Literature; to: PMID: 41014130 Rips et al 2025 report a newborn of consanguineous non-AJ ancestry with severe costovertebral malformations, dysmorphism and homozygous LoF DMRT2 variant identified on singleton exome sequencing (no parental testing). The patient also had congenital heart disease, bilateral duplicated kidneys, cleft palate, inguinal hernias.This patient also had immunodeficiency with thymic aplasia, absence of TRECs on NBS, profound lymphopenia with death at 3 months of age from CMV pneumonitis. Prenatal features include severe polyhydramnios.

PMID: 29681102 Bouman et al 2018 report a male neonate of consanguineous North African descent with thoracic vertebral anomalies, rib anomalies, dysmorphism and severe respiratory deficiency resulting in neonatal death at 9 days of age. Extra-skeletal anomalies included aberrate right subclavian artery, non-functional left kidney and tetehterd cord.Prenatal features included increased NT (8.0mm), scoliosis (15+4 weeks), IUGR/kyphoscoliosis/small thoracic cage (28+2 weeks). Trio WES identified a homozygous start-loss DMRT2 variant (c.1A>T p.Met1?) classified as a VUS. In addition, a homozygous canonical acceptor site variant in the non-canonical transcript was detected in SH3PXD2B associated with Frank-Ter Haar syndrome which is also known to have skeletal features including rarely respiratory failure leading to neonatal death (PMID: 31978614). The parents were heterozygous for both sets of variants and the unaffected sibling was homozygous wild-type.

PMID: 16387892 Seo et al 2006 report a knockout mouse model with abnormal rib and sternal development, respiratory insufficiency.

Overlapping features between the 2 unrelated patients and the mouse model include severe skeletal manifestations. However, one of the reported cases also had an alternative genomic finding relevant to skeletal issues. Other overlapping features observed in the 2 patients and not in the mouse include congenital heart defects and CAKUT.
Sources: Literature
Mendeliome v1.3296 DMRT2 Krithika Murali Classified gene: DMRT2 as Green List (high evidence)
Mendeliome v1.3296 DMRT2 Krithika Murali Gene: dmrt2 has been classified as Green List (High Evidence).
Mendeliome v1.3295 DMRT2 Krithika Murali changed review comment from: PMID: 41014130 Rips et al 2025 report a newborn of consanguineous non-AJ ancestry with severe costovertebral malformations, dysmorphism and homozygous LoF DMRT2 variant identified on singleton exome sequencing (no parental testing). The patient also had congenital heart disease, bilateral duplicated kidneys, cleft palate, inguinal hernias.This patient also had immunodeficiency with thymic aplasia, absence of TRECs on NBS, profound lymphopenia with death at 3 months of age from CMV pneumonitis. Prenatal features include severe polyhydramnios.

PMID: 29681102 Bouman et al 2018 report a male neonate of consanguineous North African descent with thoracic vertebral anomalies, rib anomalies, dysmorphism and severe respiratory deficiency resulting in neonatal death at 9 days of age. Extra-skeletal anomalies included aberrate right subclavian artery, non-functional left kidney and tetehterd cord.Prenatal features included increased NT (8.0mm), scoliosis (15+4 weeks), IUGR/kyphoscoliosis/small thoracic cage (28+2 weeks). Trio WES identified a homozygous start-loss DMRT2 variant (c.1A>T p.Met1?) classified as a VUS. In addition, a homozygous canonical acceptor site variant in the non-canonical transcript was detected in SH3PXD2B associated with Fran Ter Haar syndrome which is also known to have skeletal features. The parents were heterozygous for both sets of variants and the unaffected sibling was homozygous wild-type.

PMID: 16387892 Seo et al 2006 report a knockout mouse model with abnormal rib and sternal development, respiratory insufficiency.

Overlapping features between the 2 unrelated patients and the mouse model include severe skeletal manifestations. However, one of the reported cases also had an alternative genomic finding relevant to skeletal issues. Other overlapping features observed in the 2 patients and not in the mouse include congenital heart defects and CAKUT.
Sources: Literature; to: PMID: 41014130 Rips et al 2025 report a newborn of consanguineous non-AJ ancestry with severe costovertebral malformations, dysmorphism and homozygous LoF DMRT2 variant identified on singleton exome sequencing (no parental testing). The patient also had congenital heart disease, bilateral duplicated kidneys, cleft palate, inguinal hernias.This patient also had immunodeficiency with thymic aplasia, absence of TRECs on NBS, profound lymphopenia with death at 3 months of age from CMV pneumonitis. Prenatal features include severe polyhydramnios.

PMID: 29681102 Bouman et al 2018 report a male neonate of consanguineous North African descent with thoracic vertebral anomalies, rib anomalies, dysmorphism and severe respiratory deficiency resulting in neonatal death at 9 days of age. Extra-skeletal anomalies included aberrate right subclavian artery, non-functional left kidney and tetehterd cord.Prenatal features included increased NT (8.0mm), scoliosis (15+4 weeks), IUGR/kyphoscoliosis/small thoracic cage (28+2 weeks). Trio WES identified a homozygous start-loss DMRT2 variant (c.1A>T p.Met1?) classified as a VUS. In addition, a homozygous canonical acceptor site variant in the non-canonical transcript was detected in SH3PXD2B associated with Frank-Ter Haar syndrome which is also known to have skeletal features including rarely respiratory failure leading to neonatal death (PMID: 31978614). The parents were heterozygous for both sets of variants and the unaffected sibling was homozygous wild-type.

PMID: 16387892 Seo et al 2006 report a knockout mouse model with abnormal rib and sternal development, respiratory insufficiency.

Overlapping features between the 2 unrelated patients and the mouse model include severe skeletal manifestations. However, one of the reported cases also had an alternative genomic finding relevant to skeletal issues. Other overlapping features observed in the 2 patients and not in the mouse include congenital heart defects and CAKUT.
Sources: Literature
Mendeliome v1.3295 DMRT2 Krithika Murali Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230; DMRT2-related to skeletal dysplasia MONDO:0018230,DMRT2-related
Mendeliome v1.3294 DMRT2 Krithika Murali Marked gene: DMRT2 as ready
Mendeliome v1.3294 DMRT2 Krithika Murali Gene: dmrt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3294 DMRT2 Krithika Murali Classified gene: DMRT2 as Amber List (moderate evidence)
Mendeliome v1.3294 DMRT2 Krithika Murali Gene: dmrt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3293 DMRT2 Krithika Murali gene: DMRT2 was added
gene: DMRT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DMRT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMRT2 were set to PMID: 41014130; 29681102; 16387292
Phenotypes for gene: DMRT2 were set to skeletal dysplasia MONDO:0018230; DMRT2-related
Review for gene: DMRT2 was set to AMBER
Added comment: PMID: 41014130 Rips et al 2025 report a newborn of consanguineous non-AJ ancestry with severe costovertebral malformations, dysmorphism and homozygous LoF DMRT2 variant identified on singleton exome sequencing (no parental testing). The patient also had congenital heart disease, bilateral duplicated kidneys, cleft palate, inguinal hernias.This patient also had immunodeficiency with thymic aplasia, absence of TRECs on NBS, profound lymphopenia with death at 3 months of age from CMV pneumonitis. Prenatal features include severe polyhydramnios.

PMID: 29681102 Bouman et al 2018 report a male neonate of consanguineous North African descent with thoracic vertebral anomalies, rib anomalies, dysmorphism and severe respiratory deficiency resulting in neonatal death at 9 days of age. Extra-skeletal anomalies included aberrate right subclavian artery, non-functional left kidney and tetehterd cord.Prenatal features included increased NT (8.0mm), scoliosis (15+4 weeks), IUGR/kyphoscoliosis/small thoracic cage (28+2 weeks). Trio WES identified a homozygous start-loss DMRT2 variant (c.1A>T p.Met1?) classified as a VUS. In addition, a homozygous canonical acceptor site variant in the non-canonical transcript was detected in SH3PXD2B associated with Fran Ter Haar syndrome which is also known to have skeletal features. The parents were heterozygous for both sets of variants and the unaffected sibling was homozygous wild-type.

PMID: 16387892 Seo et al 2006 report a knockout mouse model with abnormal rib and sternal development, respiratory insufficiency.

Overlapping features between the 2 unrelated patients and the mouse model include severe skeletal manifestations. However, one of the reported cases also had an alternative genomic finding relevant to skeletal issues. Other overlapping features observed in the 2 patients and not in the mouse include congenital heart defects and CAKUT.
Sources: Literature
Mendeliome v1.3292 GTF2I Zornitza Stark Classified gene: GTF2I as Green List (high evidence)
Mendeliome v1.3292 GTF2I Zornitza Stark Gene: gtf2i has been classified as Green List (High Evidence).
Mendeliome v1.3291 GTF2I Zornitza Stark gene: GTF2I was added
gene: GTF2I was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GTF2I was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GTF2I were set to 40962490
Phenotypes for gene: GTF2I were set to Neurodevelopmental disorder MONDO:0700092, GTF2I-related
Review for gene: GTF2I was set to GREEN
Added comment: 7 individuals reported with de novo variants in this gene and a neurodevelopmental disorder. All but one of the variants are absent from gnomAD v4 (one het present for the indel variant).
Sources: Literature
Mendeliome v1.3290 BBOX1 Zornitza Stark Marked gene: BBOX1 as ready
Mendeliome v1.3290 BBOX1 Zornitza Stark Gene: bbox1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3290 BBOX1 Zornitza Stark Classified gene: BBOX1 as Amber List (moderate evidence)
Mendeliome v1.3290 BBOX1 Zornitza Stark Gene: bbox1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3289 BBOX1 Zornitza Stark gene: BBOX1 was added
gene: BBOX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BBOX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBOX1 were set to 41022783
Phenotypes for gene: BBOX1 were set to Carnitine deficiency, MONDO:0017716, BBOX1-related
Review for gene: BBOX1 was set to AMBER
Added comment: Three individuals from two unrelated families reported, presenting with myopathy, neurodevelopmental delay, and later-onset psychiatric manifestations. C. elegans knockout and patient-variant models show embryonic lethality rescued by L‑carnitine supplementation
Sources: Literature
Mendeliome v1.3288 CPD Sarah Milton changed review comment from: CPD encodes carboxypeptidase D which is part of the metallocarboxylpeptidases family. These enzymes are zinc dependent and cleave c terminal arginine and lysine. Which in turn has a role in production of nitric oxide which is known to play role in the cochlea.

PMID: 41026541 describes 5 individuals from 3 families with biallelic missense variants in CPD who have prelingual onset bilateral profound SNHL. No syndromic features were noted in affected probands.
All variants appropriately rare in gnomad v4 for a rare recessive disorder.
No homozygous loss of function variants in gene in gnomad v4.

Functional studies demonstrated reduction in nitric oxide levels in patient cells as well as increased apoptosis with rescue upon introduction on L arginine. Proposed mechanism of disease is loss of function.
Drosophila studies demonstrated disrupted Johnston’s organ morphology and impaired auditory transduction with partial rescue by arginine. Other supportive functional models discussed in paper.

Authors suggest potential treatment of affected individuals with arginine supplementation.
Sources: Literature; to: CPD encodes carboxypeptidase D which is part of the metallocarboxylpeptidases family. These enzymes are zinc dependent and cleave c terminal arginine and lysine. Which in turn has a role in production of nitric oxide which is known to play role in the cochlea.

PMID: 41026541 describes 5 individuals from 3 families with biallelic missense variants in CPD who have prelingual onset bilateral profound SNHL. No syndromic features were noted in affected probands.
All variants appropriately rare in gnomad v4 for a rare recessive disorder.
No homozygous loss of function variants in gene in gnomad v4.
All families consanguineous.

Functional studies demonstrated reduction in nitric oxide levels in patient cells as well as increased apoptosis with rescue upon introduction on L arginine. Proposed mechanism of disease is loss of function.
Drosophila studies demonstrated disrupted Johnston’s organ morphology and impaired auditory transduction with partial rescue by arginine. Other supportive functional models discussed in paper.

Authors suggest potential treatment of affected individuals with arginine supplementation.
Sources: Literature
Mendeliome v1.3288 CPD Sarah Milton gene: CPD was added
gene: CPD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPD were set to PMID: 41026541
Phenotypes for gene: CPD were set to Nonsyndromic genetic hearing loss, MONDO:0019497, CPD-related
Review for gene: CPD was set to GREEN
Added comment: CPD encodes carboxypeptidase D which is part of the metallocarboxylpeptidases family. These enzymes are zinc dependent and cleave c terminal arginine and lysine. Which in turn has a role in production of nitric oxide which is known to play role in the cochlea.

PMID: 41026541 describes 5 individuals from 3 families with biallelic missense variants in CPD who have prelingual onset bilateral profound SNHL. No syndromic features were noted in affected probands.
All variants appropriately rare in gnomad v4 for a rare recessive disorder.
No homozygous loss of function variants in gene in gnomad v4.

Functional studies demonstrated reduction in nitric oxide levels in patient cells as well as increased apoptosis with rescue upon introduction on L arginine. Proposed mechanism of disease is loss of function.
Drosophila studies demonstrated disrupted Johnston’s organ morphology and impaired auditory transduction with partial rescue by arginine. Other supportive functional models discussed in paper.

Authors suggest potential treatment of affected individuals with arginine supplementation.
Sources: Literature
Mendeliome v1.3288 JPH2 Melanie Marty reviewed gene: JPH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30384889, 31227780, 32870709, 35838873, 32879264, 34036930, 23715556, 29540472, 35288587, 37461109, 30847666, 27471098, 23715556; Phenotypes: Cardiomyopathy, hypertrophic, MIM#613873, Cardiomyopathy, dilated, 2E, MIM# 619492; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3288 LEMD2 Bryony Thompson Classified gene: LEMD2 as Green List (high evidence)
Mendeliome v1.3288 LEMD2 Bryony Thompson Added comment: Comment on list classification: Biallelic cataract/cardiomyopathy association Amber & Monoallelic recurrent de novo progeroid syndrome association Green.
Mendeliome v1.3288 LEMD2 Bryony Thompson Gene: lemd2 has been classified as Green List (High Evidence).
Mendeliome v1.3287 LEMD2 Bryony Thompson reviewed gene: LEMD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38757373, 37867468, 30905398; Phenotypes: Marbach-Rustad progeroid syndrome MONDO:0859147; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3287 INPP4A Zornitza Stark Publications for gene: INPP4A were set to 31978615; 31938306; 25338135; 20011524
Mendeliome v1.3286 INPP4A Zornitza Stark Phenotypes for gene: INPP4A were changed from Intellectual disability to Neurodevelopmental disorder with growth impairment, quadriparesis, and poor or absent speech, MIM# 621354
Mendeliome v1.3285 INPP4A Zornitza Stark edited their review of gene: INPP4A: Changed phenotypes: Neurodevelopmental disorder with growth impairment, quadriparesis, and poor or absent speech, MIM# 621354
Mendeliome v1.3285 PLD4 Zornitza Stark Phenotypes for gene: PLD4 were changed from Systemic lupus erythematosus - MONDO:0007915, PLD4-related to Systemic lupus erythematosus 18, MIM# 621369
Mendeliome v1.3284 PLD4 Zornitza Stark reviewed gene: PLD4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Systemic lupus erythematosus 18, MIM# 621369; Mode of inheritance: None
Mendeliome v1.3284 IL17RD Bryony Thompson Classified gene: IL17RD as Red List (low evidence)
Mendeliome v1.3284 IL17RD Bryony Thompson Gene: il17rd has been classified as Red List (Low Evidence).
Mendeliome v1.3283 RHOBTB2 Lucy Spencer reviewed gene: RHOBTB2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Complex neurodevelopmental disorder MONDO:0100038, RHOBTB2-related; Mode of inheritance: None
Mendeliome v1.3283 RHOB Lucy Spencer edited their review of gene: RHOB: Changed phenotypes: Cerebral palsy MONDO:0006497, RHOB-related
Mendeliome v1.3283 RHOB Lucy Spencer changed review comment from: Adding a MONDO term cerebral palsy MONDO:000649, RHOB-related; to: Adding a MONDO term cerebral palsy MONDO:0006497, RHOB-related
Mendeliome v1.3283 RHOB Lucy Spencer reviewed gene: RHOB: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral palsy MONDO:000649, RHOB-related; Mode of inheritance: None
Mendeliome v1.3283 RHBDF2 Lucy Spencer reviewed gene: RHBDF2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency disease MONDO:0021094, RHBDF2-related; Mode of inheritance: None
Mendeliome v1.3283 RHBDF1 Lucy Spencer reviewed gene: RHBDF1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy MONDO:0005021, RHBDF1-related; Mode of inheritance: None
Mendeliome v1.3283 RGS9BP Lucy Spencer reviewed gene: RGS9BP: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Prolonged electroretinal response suppression 2 MIM#620344; Mode of inheritance: None
Mendeliome v1.3283 RGS9 Lucy Spencer reviewed gene: RGS9: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Prolonged electroretinal response suppression 1 MIM#608415; Mode of inheritance: None
Mendeliome v1.3283 RGS10 Lucy Spencer reviewed gene: RGS10: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency disease MONDO:0021094, RGS10-related; Mode of inheritance: None
Mendeliome v1.3283 RFXAP Lucy Spencer reviewed gene: RFXAP: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: MHC class II deficiency 4 MIM#620817; Mode of inheritance: None
Mendeliome v1.3283 RFX5 Lucy Spencer reviewed gene: RFX5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: MHC class II deficiency 5 MIM#620818, MHC class II deficiency 3 MIM#620816; Mode of inheritance: None
Mendeliome v1.3283 REV3L Lucy Spencer reviewed gene: REV3L: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Mobius syndrome MONDO:0008006, REV3L-related; Mode of inheritance: None
Mendeliome v1.3283 REN Lucy Spencer reviewed gene: REN: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Tubulointerstitial kidney disease, autosomal dominant, 4 MIM#613092; Mode of inheritance: None
Mendeliome v1.3283 RELA Lucy Spencer reviewed gene: RELA: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory disease, familial, Behcet-like-3 MIM#618287; Mode of inheritance: None
Mendeliome v1.3283 REEP2 Lucy Spencer reviewed gene: REEP2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 72B, autosomal recessive MIM#620606, Spastic paraplegia 72A, autosomal dominant MIM#615625; Mode of inheritance: None
Mendeliome v1.3283 RECQL4 Lucy Spencer reviewed gene: RECQL4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: RECON progeroid syndrome MONDO:0957266, RECQL4-related; Mode of inheritance: None
Mendeliome v1.3283 RECQL Lucy Spencer reviewed gene: RECQL: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: RECON progeroid syndrome MIM#620370; Mode of inheritance: None
Mendeliome v1.3283 RDH12 Lucy Spencer reviewed gene: RDH12: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: RDH12-related recessive retinopathy MONDO:0800099, RDH12-related dominant retinopathy MONDO:0800100; Mode of inheritance: None
Mendeliome v1.3283 RCAN1 Lucy Spencer reviewed gene: RCAN1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Focal segmental glomerulosclerosis MONDO:0100313, RCAN1-related; Mode of inheritance: None
Mendeliome v1.3283 RC3H1 Lucy Spencer reviewed gene: RC3H1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Immune dysregulation and systemic hyperinflammation syndrome MIM#618998, Inborn error of immunity, MONDO:0003778, RC3H1-related; Mode of inheritance: None
Mendeliome v1.3283 RBM7 Lucy Spencer reviewed gene: RBM7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy MONDO:0001516, RBM7-related; Mode of inheritance: None
Mendeliome v1.3283 REC8 Lucy Spencer reviewed gene: REC8: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ovarian failure MONDO:0005387, REC8-related; Mode of inheritance: None
Mendeliome v1.3283 BCL11B Zornitza Stark Publications for gene: BCL11B were set to 29985992
Mendeliome v1.3282 ADGRV1 Zornitza Stark Phenotypes for gene: ADGRV1 were changed from Febrile seizures, familial, 4 MIM#604352; Usher syndrome, type 2C MIM#60547; Usher syndrome, type 2C, GPR98/PDZD7 digenic MIM#605472 to Epilepsy, MONDO:0005027, ADGRV1-related; Usher syndrome, type 2C MIM#60547; Usher syndrome, type 2C, GPR98/PDZD7 digenic MIM#605472
Mendeliome v1.3281 ADGRV1 Zornitza Stark Publications for gene: ADGRV1 were set to 22147658, 25572244, 14740321
Mendeliome v1.3280 ADGRV1 Zornitza Stark Mode of inheritance for gene: ADGRV1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3279 ADGRV1 Zornitza Stark reviewed gene: ADGRV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29266188, 29261713, 32962041, 34160719, 40673693, 40217298, 36399868, 34744978; Phenotypes: Epilepsy, MONDO:0005027, ADGRV1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3279 DNM1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNM1.
Source Literature was added to DNM1.
Publications for gene DNM1 were changed from 25262651; 27066543; 33372033; 34172529; 36553519; 37900685 to 25262651; 27066543; 33372033; 34172529; 36553519; 37900685
Mendeliome v1.3278 B9D1 Zornitza Stark Phenotypes for gene: B9D1 were changed from Joubert syndrome 27, MIM#617120; Meckel syndrome 9, MIM#614209 to Ciliopathy, MONDO:0005308, B9D1-related
Mendeliome v1.3277 B9D1 Zornitza Stark Publications for gene: B9D1 were set to 24886560; 21493627; 25920555; 21763481; 34338422
Mendeliome v1.3276 RNF31 Zornitza Stark Publications for gene: RNF31 were set to 26008899; 30936877
Mendeliome v1.3275 RNF31 Zornitza Stark Classified gene: RNF31 as Green List (high evidence)
Mendeliome v1.3275 RNF31 Zornitza Stark Gene: rnf31 has been classified as Green List (High Evidence).
Mendeliome v1.3274 RNF31 Zornitza Stark edited their review of gene: RNF31: Added comment: Two more families reported.; Changed rating: GREEN; Changed publications: 26008899, 30936877, 39009172, 41026334
Mendeliome v1.3274 DNAJC5 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAJC5.
Source Expert list was added to DNAJC5.
Phenotypes for gene: DNAJC5 were changed from Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant - MIM#162350; ceroid lipofuscinosis, neuronal, 4 (Kufs type) - MONDO:0008083 to Ceroid lipofuscinosis, neuronal, 4 (Kufs type), MONDO:0008083
Mendeliome v1.3273 RASA2 Zornitza Stark Phenotypes for gene: RASA2 were changed from to Noonan syndrome MONDO:0018997, RASA2-related
Mendeliome v1.3272 RAP1A Zornitza Stark Phenotypes for gene: RAP1A were changed from Kabuki syndrome to Kabuki syndrome MONDO:0016512, RAP1A-related
Mendeliome v1.3271 RAMP2 Zornitza Stark Phenotypes for gene: RAMP2 were changed from Primary open angle glaucoma to Open angle glaucoma MONDO:0005338, RAMP2-related
Mendeliome v1.3270 DDB1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DDB1.
Source Literature was added to DDB1.
Phenotypes for gene: DDB1 were changed from White-Kernohan syndrome, MIM# 619426; Syndromic intellectual disability to White-Kernohan syndrome, MIM# 619426
Mendeliome v1.3270 RALGAPA1 Zornitza Stark Phenotypes for gene: RALGAPA1 were changed from Intellectual disability; hypotonia; infantile spasms. to Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation MIM#618797
Mendeliome v1.3269 RAG2 Zornitza Stark Phenotypes for gene: RAG2 were changed from Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457; Combined cellular and humoral immune defects with granulomas MIM# 233650 to Recombinase activating gene 2 deficiency MONDO:0000573
Mendeliome v1.3268 RAG1 Zornitza Stark Phenotypes for gene: RAG1 were changed from Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457 to Recombinase activating gene 1 deficiency MONDO:0000572
Mendeliome v1.3267 DNM2 Chirag Patel Phenotypes for gene: DNM2 were changed from Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482; Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; MONDO:0011674; Centronuclear myopathy 1, MIM# 160150; Lethal congenital contracture syndrome 5, MIM# 615368 to Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482; Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; MONDO:0011674; Autosomal dominant centronuclear myopathy MONDO:0008048; Lethal congenital contracture syndrome 5, MIM# 615368
Mendeliome v1.3266 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from Mental retardation, autosomal dominant 48, MIM# 617751 to Intellectual developmental disorder, autosomal dominant 48 MIM#617751
Mendeliome v1.3265 RABL2A Zornitza Stark Phenotypes for gene: RABL2A were changed from male infertility; ciliopathy to Infertility disorder, MONDO:0005047, RABL2A-related
Mendeliome v1.3264 RAB14 Zornitza Stark Phenotypes for gene: RAB14 were changed from Developmental disorders to Neurodevelopmental disorder MONDO:0700092, RAB14-related
Mendeliome v1.3263 DNM2 Chirag Patel Phenotypes for gene: DNM2 were changed from Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482; Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; MONDO:0011674; Lethal congenital contracture syndrome 5, MIM# 615368 to Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482; Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; MONDO:0011674; Centronuclear myopathy 1, MIM# 160150; Lethal congenital contracture syndrome 5, MIM# 615368
Mendeliome v1.3262 DNM2 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNM2.
Source Expert list was added to DNM2.
Phenotypes for gene: DNM2 were changed from Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482; Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; MONDO:0011674 to Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482; Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; MONDO:0011674; Lethal congenital contracture syndrome 5, MIM# 615368
Mendeliome v1.3261 PJA1 Zornitza Stark Phenotypes for gene: PJA1 were changed from Intellectual disability; trigonocephaly to X-linked complex neurodevelopmental disorder, PJA1-related, MONDO:0100148
Mendeliome v1.3260 NDE1 Zornitza Stark Phenotypes for gene: NDE1 were changed from Microhydranencephaly 605013; Lissencephaly 4 (with microcephaly) 614019 to Microcephaly with lissencephaly and/or hydranencephaly, MONDO:0700116
Mendeliome v1.3259 DALRD3 Chirag Patel Phenotypes for gene: DALRD3 were changed from Epileptic encephalopathy; Epileptic encephalopathy, early infantile, 86 618910 to Developmental and epileptic encephalopathy, 86 MONDO:0030054
Mendeliome v1.3258 NEK9 Zornitza Stark Phenotypes for gene: NEK9 were changed from Lethal congenital contracture syndrome 10, MIM# 617022; Arthrogryposis, Perthes disease, and upward gaze palsy, MIM# 614262; Skeletal dysplasia to NEK9-related lethal skeletal dysplasia MONDO:0014870; Lethal congenital contracture syndrome 10, MIM# 617022; Arthrogryposis, Perthes disease, and upward gaze palsy, MIM# 614262; Skeletal dysplasia
Mendeliome v1.3257 DMGDH Chirag Patel Source Victorian Clinical Genetics Services was removed from DMGDH.
Source Expert list was added to DMGDH.
Phenotypes for gene: DMGDH were changed from Dimethylglycine dehydrogenase deficiency MIM#605850; Disorders and variants of other enzymes that oxidise xenobiotics to Dimethylglycine dehydrogenase deficiency MIM#605850
Mendeliome v1.3256 DMGDH Chirag Patel Classified gene: DMGDH as Red List (low evidence)
Mendeliome v1.3256 DMGDH Chirag Patel Gene: dmgdh has been classified as Red List (Low Evidence).
Mendeliome v1.3255 DMGDH Chirag Patel reviewed gene: DMGDH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dimethylglycine dehydrogenase deficiency MONDO:0011610; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3255 DAB1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DAB1.
Phenotypes for gene: DAB1 were changed from Spinocerebellar ataxia 37 MIM#615945; Ataxia and intellectual disability to Spinocerebellar ataxia 37 MIM#615945; Neurodevelopmental disorder, MONDO:0700092, DAB1-related
Mendeliome v1.3254 DMC1 Chirag Patel Phenotypes for gene: DMC1 were changed from Primary ovarian failure, MONDO:0005387,; Azoospermia, MONDO:010045 to Primary ovarian failure, MONDO:0005387, Azoospermia, MONDO:0100459, DMC1-related
Publications for gene DMC1 were changed from 34794894, 18166824, 29331980, 9660954, 9660953 to 34794894, 18166824, 29331980, 9660954, 9660953
Mendeliome v1.3253 DNAJA1 Chirag Patel Phenotypes for gene: DNAJA1 were changed from Intellectual disability; seizures to Neurodevelopmental disorder, MONDO:0700092, DNAJA1-related
Mendeliome v1.3252 DMC1 Chirag Patel Phenotypes for gene: DMC1 were changed from Primary ovarian insufficiency; non-obstructive azoospermia to Primary ovarian failure, MONDO:0005387,; Azoospermia, MONDO:010045
Mendeliome v1.3251 DLK1 Chirag Patel Phenotypes for gene: DLK1 were changed from central precocious puberty to central precocious puberty, MONDO:0019165
Mendeliome v1.3250 DGCR8 Chirag Patel Phenotypes for gene: DGCR8 were changed from Schwannoma, MONDO:0002546 to Schwannoma, MONDO:0002546; Early-onset multinodular goiter and schwannomatosis, no MIM#
Mendeliome v1.3249 DGCR8 Chirag Patel reviewed gene: DGCR8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Schwannoma, MONDO:0002546, Early-onset multinodular goiter and schwannomatosis, no MIM#; Mode of inheritance: None
Mendeliome v1.3248 DGCR8 Chirag Patel Source Literature was removed from DGCR8.
Source Expert list was added to DGCR8.
Phenotypes for gene: DGCR8 were changed from Early-onset multinodular goiter and schwannomatosis to Schwannoma, MONDO:0002546
Mendeliome v1.3247 DHX34 Chirag Patel Phenotypes for gene: DHX34 were changed from Intellectual disability; congenital anomalies to Neurodevelopmental disorder, MONDO:0700092, DHX34-related
Mendeliome v1.3245 DLG1 Chirag Patel Phenotypes for gene: DLG1 were changed from Non-syndromic cleft lip and palate to cleft lip/palate MONDO:0016044
Mendeliome v1.3244 DNMBP Chirag Patel Phenotypes for gene: DNMBP were changed from congenital cataract to Cataract 48, MIM#618415
Mendeliome v1.3243 DNAJB11 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAJB11.
Source Expert list was added to DNAJB11.
Publications for gene DNAJB11 were changed from 29706351, 29777155, 32631624, 35664268, 32775842, 33129895, 34177435 to 29706351, 29777155, 32631624, 35664268, 32775842, 33129895, 34177435
Mendeliome v1.3242 ACTG1 Chirag Patel Source Victorian Clinical Genetics Services was removed from ACTG1.
Source Expert list was added to ACTG1.
Publications for gene ACTG1 were changed from PMID: 29620237, 22366783, 25052316, 28493397, 26188271, 27240540, 13680526, 14684684, 16773128, 19477959, 19497859 to PMID: 29620237, 22366783, 25052316, 28493397, 26188271, 27240540, 13680526, 14684684, 16773128, 19477959, 19497859
Mendeliome v1.3241 BCL11B Sarah Milton reviewed gene: BCL11B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40033098, 37860968, 37337996; Phenotypes: Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities, MONDO:0060763; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3241 ADGRV1 Chirag Patel Source Victorian Clinical Genetics Services was removed from ADGRV1.
Source Expert list was added to ADGRV1.
Publications for gene ADGRV1 were changed from 22147658, 25572244, 14740321 to 22147658, 25572244, 14740321
Mendeliome v1.3240 AFP Chirag Patel Publications for gene AFP were changed from 15280901; 18854864, 14699509, 7684942 to 15280901; 18854864, 14699509, 7684942
Mendeliome v1.3239 AFP Chirag Patel Source Victorian Clinical Genetics Services was removed from AFP.
Source Literature was added to AFP.
Mode of inheritance for gene AFP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3238 AFP Chirag Patel reviewed gene: AFP: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 14699509, 7684942; Phenotypes: [Hereditary persistence of alpha-fetoprotein] MIM#615970; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3238 B9D1 Sarah Milton reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40565534, 40933483; Phenotypes: Ciliopathy, MONDO:0005308, B9D1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3238 B9D1 Sarah Milton Deleted their review
Mendeliome v1.3238 B9D1 Sarah Milton reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40565534, 40933483; Phenotypes: Ciliopathy, MONDO:0005308, B9D1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3238 AKT2 Chirag Patel Source Victorian Clinical Genetics Services was removed from AKT2.
Source Literature was added to AKT2.
Phenotypes for gene: AKT2 were changed from Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416; Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Diabetes mellitus, type II , MIM#125853 to Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416; AKT2-related familial partial lipodystrophy MONDO:0019192
Mendeliome v1.3237 ALG2 Chirag Patel Classified gene: ALG2 as Green List (high evidence)
Mendeliome v1.3237 ALG2 Chirag Patel Gene: alg2 has been classified as Green List (High Evidence).
Mendeliome v1.3236 ALG2 Chirag Patel reviewed gene: ALG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12684507, 34980536, 23404334, 30397276, 33644825; Phenotypes: Congenital disorder of glycosylation, type Ii, MIM# 607906; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3236 RASA2 Lucy Spencer reviewed gene: RASA2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome MONDO:0018997, RASA2-related; Mode of inheritance: None
Mendeliome v1.3236 RAP1A Lucy Spencer reviewed gene: RAP1A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Kabuki syndrome MONDO:0016512, RAP1A-related; Mode of inheritance: None
Mendeliome v1.3236 RAMP2 Lucy Spencer reviewed gene: RAMP2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Open angle glaucoma MONDO:0005338, RAMP2-related; Mode of inheritance: None
Mendeliome v1.3236 RALGAPA1 Lucy Spencer reviewed gene: RALGAPA1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation MIM#618797; Mode of inheritance: None
Mendeliome v1.3236 RAG2 Lucy Spencer reviewed gene: RAG2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Recombinase activating gene 2 deficiency MONDO:0000573; Mode of inheritance: None
Mendeliome v1.3236 RAG1 Lucy Spencer reviewed gene: RAG1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Recombinase activating gene 1 deficiency MONDO:0000572; Mode of inheritance: None
Mendeliome v1.3236 RAC1 Lucy Spencer reviewed gene: RAC1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 48 MIM#617751; Mode of inheritance: None
Mendeliome v1.3236 RABL2A Lucy Spencer reviewed gene: RABL2A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Infertility disorder, MONDO:0005047, RABL2A-related; Mode of inheritance: None
Mendeliome v1.3236 RAB14 Lucy Spencer reviewed gene: RAB14: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder MONDO:0700092, RAB14-related; Mode of inheritance: None
Mendeliome v1.3236 NDP Zornitza Stark Phenotypes for gene: NDP were changed from Exudative vitreoretinopathy 2, X-linked, MIM 305390; Norrie disease, MIM 310600 to Norrie disease MONDO:0010691; Exudative vitreoretinopathy 2, X-linked, MIM 305390; Norrie disease, MIM 310600
Mendeliome v1.3235 AP2S1 Zornitza Stark Phenotypes for gene: AP2S1 were changed from Hypocalciuric hypercalcaemia, type III, MIM# 600740; MONDO:0010926; Developmental disorder to Hypocalciuric hypercalcaemia, type III, MIM# 600740; MONDO:0010926; Neurodevelopmental disorder, MONDO:0700092, AP2S1-related
Mendeliome v1.3234 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to 33057194; 23222959; 33729479; 33168530; 3204769; 31723423; 29479578
Mendeliome v1.3233 AP2S1 Zornitza Stark edited their review of gene: AP2S1: Added comment: Association with NDD: Several isolated cases with de novo missense variants in large NDD cohorts PMID: 31981491;33057194;35982160;35982159.

26 unrelated NDD in a preprint with 5 recurring de novo missenses p.Arg10Trp, p.Arg10Gln, p.Lys18Glu, p.Lys18Asn and p.Arg61His https://doi.org/10.1101/2024.07.22.24310683. 70% had epilepsy, 50% brain anomalies.; Changed publications: 23222959, 33729479, 33168530, 3204769, 31723423, 29479578, 31981491, 33057194, 35982160, 35982159; Changed phenotypes: Hypocalciuric hypercalcaemia, type III, MIM# 600740, MONDO:0010926, Neurodevelopmental disorder, MONDO:0700092, AP2S1-related
Mendeliome v1.3232 GPHN Bryony Thompson Phenotypes for gene: GPHN were changed from Molybdenum cofactor deficiency C, MIM# 615501; Epilepsy; Autism; Intellectual disability to sulfite oxidase deficiency due to molybdenum cofactor deficiency type C MONDO:0014212; complex neurodevelopmental disorder MONDO:0100038
Mendeliome v1.3231 GPHN Bryony Thompson Publications for gene: GPHN were set to 22040219; 11095995; 26613940; 24561070; 23393157; 27604308; 9812897
Mendeliome v1.3230 GPHN Bryony Thompson edited their review of gene: GPHN: Added comment: High evidence - AR Molybdenum cofactor deficiency C - PMID: 22040219, 11095995, 9812897, 34617111 - now 3 unrelated families and a mouse model. LoF is the mechanism of disease.

Amber - AD complex neurodevelopmental disorder - PMID: 26613940, 24561070, 23393157 - de novo missense and de novo/inherited deletions with supporting functional assays. However, incomplete penetrance has been reported for some of the CNVs.; Changed publications: 11095995, 22040219, 9812897, 34617111, 26613940, 24561070, 23393157; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3229 MT-ATP6 Zornitza Stark Publications for gene: MT-ATP6 were set to 40112238
Mendeliome v1.3228 MT-ATP6 Zornitza Stark edited their review of gene: MT-ATP6: Added comment: DEFINITIVE by ClinGen.; Changed publications: 40112238, 1550128, 8554662, 23206802, 1456751, 9270604, 9501263, 10604142, 17352390, 11245730, 16217706, 11731285, 27812026, 25037980, 19747204, 2137962
Mendeliome v1.3228 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Mendeliome v1.3228 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Mendeliome v1.3228 MT-TY Zornitza Stark Classified gene: MT-TY as Green List (high evidence)
Mendeliome v1.3228 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Mendeliome v1.3227 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Review for gene: MT-TY was set to GREEN
Added comment: DEFINITIVE by ClinGen.

Multiple individuals reported. Age of onset in affected individuals is variable and clinical features seen include myopathy with or without ophthalmoplegia. There is at least one case report with a more severe phenotype with neuropathy, ataxia, seizures, myoclonus, sensorineural hearing loss, and pigmentary retinopathy. Muscle biopsy in affected individuals has shown COX-negative and ragged red fibers, with variable mitochondrial respiratory chain enzyme deficiencies. The variants in affected individuals are often present at highest heteroplasmy levels in muscle and may be undetectable in other tissues such as blood and buccal tissue. Multiple single fiber studies were performed in these patients and supportive of variant pathogenicity
Sources: Expert list
Mendeliome v1.3226 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Mendeliome v1.3226 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Mendeliome v1.3226 MT-TW Zornitza Stark Classified gene: MT-TW as Green List (high evidence)
Mendeliome v1.3226 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Mendeliome v1.3225 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Review for gene: MT-TW was set to GREEN
Added comment: DEFINITIVE by ClinGen.

At least 10 individuals reported. Age of onset in affected individuals ranged from childhood to adulthood. Clinical features in affected individuals included LSS, microcephaly, developmental delay and regression, cognitive decline, fatigue, seizures, ataxia, chorea, muscle wasting, axonal neuropathy, diabetes, liver steatosis and fibrosis, constipation, recurrent vomiting, failure to thrive, pigmentary retinopathy, ptosis, optic atrophy, ophthalmoplegia, sensorineural hearing loss, and hypertrophic and dilated cardiomyopathy. Brain imaging was variable and ranged from normal to findings consistent with LSS to generalized atrophy and white matter involvement.

Muscle biopsies showed ragged red fibers, COX-deficient fibers, and decreased respiratory chain enzyme activities. Metabolic laboratory investigations revealed elevated blood and cerebrospinal fluid lactate. Heteroplasmy levels in affected individuals were highest in muscle and/or liver when multiple tissues were assessed (25 - >95 % in muscle, 1 to >95% in blood, >95% in liver, 1-92% in skin fibroblasts, and 5% in urine when assessed). Functional studies to support variant pathogenicity.
Sources: Expert list
Mendeliome v1.3224 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Mendeliome v1.3224 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Mendeliome v1.3224 MT-TV Zornitza Stark Classified gene: MT-TV as Green List (high evidence)
Mendeliome v1.3224 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Mendeliome v1.3223 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Review for gene: MT-TV was set to GREEN
Added comment: DEFINITIVE by ClinGen.

At least 8 individuals reported. Age of onset in affected individuals ranged from childhood to adulthood. Clinical features in affected individuals included LSS, cognitive decline, fatigue, migraines, seizures, myoclonic jerks, ataxia, dystonia, dysarthria, imbalance, muscle weakness, axonal sensorimotor polyneuropathy, diabetes, gastrointestinal dysmotility, cataracts, retinitis pigmentosa, sensorineural hearing loss, and hypertrophic cardiomyopathy. Brain imaging was variable and ranged from normal to findings consistent with LSS, cerebellar and cerebral atrophy, brainstem atrophy, and basal ganglia calcifications. Muscle biopsies showed ragged red fibers, COX-deficient fibers, and normal to decreased respiratory chain enzyme activities. Metabolic laboratory investigations revealed elevated lactate.

Heteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed (67% to homoplasmic in muscle, 70% to homoplasmic in blood, and homoplasmic in skin fibroblasts).
Sources: Expert list
Mendeliome v1.3222 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Mendeliome v1.3222 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Mendeliome v1.3222 MT-TT Zornitza Stark Classified gene: MT-TT as Green List (high evidence)
Mendeliome v1.3222 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Mendeliome v1.3221 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Review for gene: MT-TT was set to GREEN
Added comment: MODERATE by ClinGen.

At least 10 probands reported with 5 unique variants. Age of onset in affected individuals varied from the neonatal period to more than 50 years. Clinical features in affected individuals included neonatal lactic acidosis; myoclonic epilepsy and ragged red fibers (MERRF); Leber Hereditary Optic Neuropathy (LHON); myopathy, seizures, migraines, pigmentary retinopathy, hearing loss, and diabetes. Brain imaging findings were variable. Muscle biopsies showed ragged red fibers and COX-deficient fibers. Lab investigations showed elevated lactate. Heteroplasmy levels were highest in muscle when multiple tissues were assessed, and ranged from 33% to homoplasmy in muscle.
Sources: Expert list
Mendeliome v1.3220 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Mendeliome v1.3220 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Mendeliome v1.3220 MT-TS2 Zornitza Stark Classified gene: MT-TS2 as Green List (high evidence)
Mendeliome v1.3220 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Mendeliome v1.3219 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Review for gene: MT-TS2 was set to GREEN
Added comment: MODERATE by ClinGen.

At least 7 individuals reported. Affected individuals had varying clinical features including cataracts, retinal dystrophy, hearing loss, myopathy, ataxia, seizures, global developmental delay, diabetes, Wolff-Parkinson-White arrhythmia, hypertrophic cardiomyopathy, and hypogonadotropic hypogonadism. Lab investigations revealed elevated blood lactate and elevated creatine kinase. Muscle biopsy, when performed, generally showed reduced activities of complexes I, I+III, III, and/or IV. Brain imaging was normal in some cases. In one individual brain imaging revealed changes in the basal ganglia and diffuse atrophy with an enlarged cisterna magna and in another showed changes in the cerebral white matter.

Heteroplasmy levels were variable – some individuals had the highest levels in muscle with the variant being undetectable in other tissues while others had the variant present at homoplasmy in multiple tissues. Northern blotting and single fiber testing further supported variant pathogenicity.
Sources: Expert list
Mendeliome v1.3218 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Mendeliome v1.3218 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Mendeliome v1.3218 MT-TS1 Zornitza Stark Classified gene: MT-TS1 as Green List (high evidence)
Mendeliome v1.3218 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Mendeliome v1.3217 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Review for gene: MT-TS1 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

At least 8 individuals reported. Clinical features seen in affected individuals range from isolated hearing loss to mitochondrial myopathy to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and myoclonus epilepsy, ragged red fibers (MERRF). One case of fatal neonatal lactic acidosis has been reported. Intrafamilial variability has been observed.

Muscle biopsy often shows COX-negative fibers and/or ragged red fibers. A combined mitochondrial chain respiratory deficiency (commonly involving complexes I and IV) may also be observed in muscle biopsies. Heteroplasmy levels in affected individuals are often near homoplasmy in muscle and lower in tissues such as blood and urine, although homoplasmy across multiple tissues has also been seen. One individual had mitochondrial myopathy with heteroplasmy levels as low as 37% heteroplasmy in muscle.

Multiple single fiber studies and cybrid analyses were performed in these patients and are supportive of variant pathogenicity.
Sources: Expert list
Mendeliome v1.3216 MT-TR Zornitza Stark Marked gene: MT-TR as ready
Mendeliome v1.3216 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Mendeliome v1.3216 MT-TR Zornitza Stark Classified gene: MT-TR as Green List (high evidence)
Mendeliome v1.3216 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Mendeliome v1.3215 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Review for gene: MT-TR was set to GREEN
Added comment: MODERATE by ClinGen.

At least 4 individuals reported. Cybrid studies and single fiber testing further supported the pathogenicity of several of the reported variants. Age of onset was in childhood and features seen in affected individuals included muscle weakness, ataxia, hypotonia, epilepsy, global developmental delay and regression, pigmentary retinopathy, optic atrophy, renal insufficiency, and hypertrophic cardiomyopathy. Muscle biopsies showed ragged red fibers and COX-negative fibers and variable respiratory chain enzyme deficiencies.
Sources: Expert list
Mendeliome v1.3214 MT-TQ Zornitza Stark Phenotypes for gene: MT-TQ were changed from to Mitochondrial disease (MONDO:0044970), MT-TQ-related
Mendeliome v1.3213 MT-TQ Zornitza Stark edited their review of gene: MT-TQ: Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TQ-related
Mendeliome v1.3213 MT-TQ Zornitza Stark Classified gene: MT-TQ as Amber List (moderate evidence)
Mendeliome v1.3213 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3212 MT-TQ Zornitza Stark gene: MT-TQ was added
gene: MT-TQ was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TQ.
Mode of inheritance for gene gene: MT-TQ was set to MITOCHONDRIAL
Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Review for gene: MT-TQ was set to AMBER
Added comment: LIMITED by ClinGen.

Three unique variants (m.4332G>A, m.4369_4370insA, m.4381A>G) reported in three probands across 3 publications. Single fiber testing further supported the pathogenicity of several of these variants. Age of onset in affected individuals was five years old, teens, and 20 years old. Clinical features in affected individuals included stroke-like episodes, hearing loss, myopathy, and Leber Hereditary Optic Neuropathy (LHON). Brain imaging was variable. Muscle biopsies showed ragged red fibers and COX-negative fibers. Metabolic screening investigations were only reported in one individual and showed high cerebrospinal fluid (CSF) lactate with normal blood lactate. Heteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed (61-87% in muscle).
Sources: Expert list
Mendeliome v1.3211 MT-TP Zornitza Stark Phenotypes for gene: MT-TP were changed from to Mitochondrial disease (MONDO:0044970), MT-TP-related
Mendeliome v1.3210 MT-TP Zornitza Stark Publications for gene: MT-TP were set to
Mendeliome v1.3209 MT-TP Zornitza Stark Tag mtDNA tag was added to gene: MT-TP.
Mendeliome v1.3209 MT-TP Zornitza Stark Classified gene: MT-TP as Green List (high evidence)
Mendeliome v1.3209 MT-TP Zornitza Stark Gene: mt-tp has been classified as Green List (High Evidence).
Mendeliome v1.3208 MT-TP Zornitza Stark reviewed gene: MT-TP: Rating: GREEN; Mode of pathogenicity: None; Publications: 7689388, 11196116, 19223931, 23696415, 19273760, 27536729, 27816331, 32305257, 32419253; Phenotypes: Mitochondrial disease (MONDO:0044970), MT-TP-related; Mode of inheritance: MITOCHONDRIAL
Mendeliome v1.3208 MT-TM Zornitza Stark Marked gene: MT-TM as ready
Mendeliome v1.3208 MT-TM Zornitza Stark Gene: mt-tm has been classified as Green List (High Evidence).
Mendeliome v1.3208 MT-TM Zornitza Stark Classified gene: MT-TM as Green List (high evidence)
Mendeliome v1.3208 MT-TM Zornitza Stark Gene: mt-tm has been classified as Green List (High Evidence).
Mendeliome v1.3207 MT-TM Zornitza Stark gene: MT-TM was added
gene: MT-TM was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TM.
Mode of inheritance for gene gene: MT-TM was set to MITOCHONDRIAL
Publications for gene: MT-TM were set to 9633749; 24711008; 25468263; 30739820; 11335700; 31488384; 31022467; 29174468
Phenotypes for gene: MT-TM were set to mitochondrial disease (MONDO:0044970), MT-TM-related
Review for gene: MT-TM was set to GREEN
Added comment: DEFINITIVE by ClinGen.

Multiple individuals reported. The condition was first described in a 10-year-old girl with exercise intolerance, myopathy, and short stature with mildly elevated serum lactate. Subsequent publications have shown a consistent phenotype involving a mitochondrial myopathy (typically childhood onset) with elevated lactate. Chronic external progressive ophthalmoplegia (CPEO) is not common but has been reported. Basal ganglia lesions and Leigh syndrome spectrum/mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) overlap have also been reported in one patient. Retinitis pigmentosa has also been reported. Muscle biopsy often shows classic findings of mitochondrial myopathy with COX-negative and ragged red (or blue) fibers. Combined OXPHOS deficiencies in muscle are also observed.
Sources: Expert list
Mendeliome v1.3206 MT-TL2 Zornitza Stark Marked gene: MT-TL2 as ready
Mendeliome v1.3206 MT-TL2 Zornitza Stark Gene: mt-tl2 has been classified as Green List (High Evidence).
Mendeliome v1.3206 MT-TL2 Zornitza Stark Classified gene: MT-TL2 as Green List (high evidence)
Mendeliome v1.3206 MT-TL2 Zornitza Stark Gene: mt-tl2 has been classified as Green List (High Evidence).
Mendeliome v1.3205 MT-TL2 Zornitza Stark gene: MT-TL2 was added
gene: MT-TL2 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TL2.
Mode of inheritance for gene gene: MT-TL2 was set to MITOCHONDRIAL
Publications for gene: MT-TL2 were set to 8923013; 12398839; 19718780; 18977334; 21819490; 15649400; 15591266; 23847141; 20022607; 29052516
Phenotypes for gene: MT-TL2 were set to Mitochondrial disease (MONDO:0044970), MT-TL2-related
Review for gene: MT-TL2 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

Multiple individuals reported with a range of clinical phenotypes, including CPEO, retinopathy, hearing loss, myopathy, exercise intolerance, and peripheral neuropathy. There is a substantial amount of functional evidence for the reported variants, including numerous single fiber studies, and respiratory chain analyses showing clear evidence of OXPHOS defects
Sources: Expert list
Mendeliome v1.3204 MT-TL1 Zornitza Stark Marked gene: MT-TL1 as ready
Mendeliome v1.3204 MT-TL1 Zornitza Stark Gene: mt-tl1 has been classified as Green List (High Evidence).
Mendeliome v1.3204 MT-TL1 Zornitza Stark Classified gene: MT-TL1 as Green List (high evidence)
Mendeliome v1.3204 MT-TL1 Zornitza Stark Gene: mt-tl1 has been classified as Green List (High Evidence).
Mendeliome v1.3203 MT-TL1 Zornitza Stark gene: MT-TL1 was added
gene: MT-TL1 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TL1.
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Publications for gene: MT-TL1 were set to 9323566; 12221518; 20471262; 23220830; 23273904; 24338029; 23582502; 11271374; 23258140
Phenotypes for gene: MT-TL1 were set to Mitochondrial disease (MONDO:0044970), MT-TL1-related
Review for gene: MT-TL1 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

Multiple individuals reported with a range of clinical presentations, including MELAS, myoclonus epilepsy, ragged red fibers (MERRF), Leigh syndrome spectrum, progressive external ophthalmoplegia (PEO), and maternally inherited deafness and diabetes (MIDD), as well as myopathy, hypertrophic cardiomyopathy, and renal disease. At least 7 unique variants reported with a substantial amount of functional evidence, including numerous cybrid analyses, single fiber studies, and respiratory chain analyses showing clear evidence of OXPHOS defects.
Sources: Expert list
Mendeliome v1.3202 MT-TK Zornitza Stark edited their review of gene: MT-TK: Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TK-related
Mendeliome v1.3202 MT-TK Zornitza Stark Phenotypes for gene: MT-TK were changed from Mitochondrial disease (MONDO:0044970), MT-TK-relatednd to Mitochondrial disease (MONDO:0044970), MT-TK-related
Mendeliome v1.3201 MT-TK Zornitza Stark Marked gene: MT-TK as ready
Mendeliome v1.3201 MT-TK Zornitza Stark Gene: mt-tk has been classified as Green List (High Evidence).
Mendeliome v1.3201 MT-TK Zornitza Stark Classified gene: MT-TK as Green List (high evidence)
Mendeliome v1.3201 MT-TK Zornitza Stark Gene: mt-tk has been classified as Green List (High Evidence).
Mendeliome v1.3200 MT-TK Zornitza Stark gene: MT-TK was added
gene: MT-TK was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TK.
Mode of inheritance for gene gene: MT-TK was set to MITOCHONDRIAL
Publications for gene: MT-TK were set to 9380435; 19618438; 17410322; 25559684; 1361099; 10868777; 35821181; 36675808
Phenotypes for gene: MT-TK were set to Mitochondrial disease (MONDO:0044970), MT-TK-relatednd
Review for gene: MT-TK was set to GREEN
Added comment: DEFINITIVE by ClinGen.

Multiple individuals reported with wide spectrum of clinical presentations including MERRF, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Leigh syndrome spectrum, and mitochondrial neurogastrointestinal encephalopathy (MNGIE), as well as lipomas, myopathy, hypertrophic cardiomyopathy, hearing loss, diabetes, and episodic ataxia. Variant pathogenicity is supported by cybrid analyses, single fiber studies, and respiratory chain studies showing clear evidence of OXPHOS defects.
Sources: Expert list
Mendeliome v1.3199 MT-TI Zornitza Stark Marked gene: MT-TI as ready
Mendeliome v1.3199 MT-TI Zornitza Stark Gene: mt-ti has been classified as Green List (High Evidence).
Mendeliome v1.3199 MT-TI Zornitza Stark Classified gene: MT-TI as Green List (high evidence)
Mendeliome v1.3199 MT-TI Zornitza Stark Gene: mt-ti has been classified as Green List (High Evidence).
Mendeliome v1.3198 MT-TI Zornitza Stark gene: MT-TI was added
gene: MT-TI was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TI.
Mode of inheritance for gene gene: MT-TI was set to MITOCHONDRIAL
Publications for gene: MT-TI were set to 15121771; 21982779; 23395828; 16120360; 9473477; 12767666; 10065021; 7646516; 20884012; 21292040; 1632786; 23696415; 34607911
Phenotypes for gene: MT-TI were set to Mitochondrial disease (MONDO:0044970), MT-TI-related
Review for gene: MT-TI was set to GREEN
Added comment: DEFINITIVE by ClinGen.

More than 10 individuals reported. Clinical presentations included LSS, myoclonic epilepsy with ragged red fibers (MERRF) and chronic progressive external ophthalmoplegia (CPEO), in addition to rhabdomyolysis, cardiomyopathy, encephalopathy, exercise intolerance, muscle weakness, hypertension2, hypercholesterolaemia, and hypomagnesaemia. Heteroplasmy levels of MT-TI can be variable in tissues from the same individual. In general, variants tend to be lower in tissues such as blood, saliva, and buccal swab and urine and muscle heteroplasmy levels tend to be higher.
Sources: Expert list
Mendeliome v1.3197 NEK9 Sangavi Sivagnanasundram reviewed gene: NEK9: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: NEK9-related lethal skeletal dysplasia MONDO:0014870; Mode of inheritance: None
Mendeliome v1.3197 MT-TH Zornitza Stark Marked gene: MT-TH as ready
Mendeliome v1.3197 MT-TH Zornitza Stark Gene: mt-th has been classified as Green List (High Evidence).
Mendeliome v1.3197 MT-TH Zornitza Stark Classified gene: MT-TH as Green List (high evidence)
Mendeliome v1.3197 MT-TH Zornitza Stark Gene: mt-th has been classified as Green List (High Evidence).
Mendeliome v1.3196 MT-TH Zornitza Stark gene: MT-TH was added
gene: MT-TH was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-TH.
Mode of inheritance for gene gene: MT-TH was set to MITOCHONDRIAL
Publications for gene: MT-TH were set to 12682337; 14967777; 15111688; 21704194; 21931169; 23696415; 35092007; 24920829; 21704194
Phenotypes for gene: MT-TH were set to Mitochondrial disease (MONDO:0044970), MT-TH-related
Review for gene: MT-TH was set to GREEN
Added comment: DEFINITIVE by ClinGen.

More than 5 individuals reported. Age of onset in affected individuals varied from adolescence to the 40s. Clinical features included stroke-like episodes, seizures, myoclonus, ataxia, optic atrophy, retinal dystrophy, cataracts, hearing loss, hypogonadism, and mood disorder. Cerebellar vermis hypoplasia and signal changes in the basal ganglia, dentate nuclei, temporal lobes, and occipital lobes were seen on brain imaging.

Tissue biopsies identified ragged red fibers and COX-negative fibers. Laboratory investigations showed increased blood and cerebrospinal fluid lactate. Decreased activities of complexes I and IV were variably seen in muscle. Heteroplasmy levels of the variants in affected individuals ranged from 81% to homoplasmic in muscle, 33-87% in urine, 1-60% in blood, and undetectable to homoplasmic in fibroblasts. Single fiber testing, cybrid analysis, and Northern blot analysis further supported variant pathogenicity.

This gene-disease relationship is also supported by known biochemical function and functional alteration in patient and non-patient cells (in vitro functional assays demonstrated reduced rates of mitochondrial translation as a result of variants in MT-TH; PMID: 24920829, 21704194).
Sources: Expert list
Mendeliome v1.3195 MT-TG Zornitza Stark Marked gene: MT-TG as ready
Mendeliome v1.3195 MT-TG Zornitza Stark Gene: mt-tg has been classified as Green List (High Evidence).
Mendeliome v1.3195 MT-TG Zornitza Stark Classified gene: MT-TG as Green List (high evidence)
Mendeliome v1.3195 MT-TG Zornitza Stark Gene: mt-tg has been classified as Green List (High Evidence).
Mendeliome v1.3194 MT-TG Zornitza Stark Tag mtDNA tag was added to gene: MT-TG.
Mendeliome v1.3194 MT-TG Zornitza Stark gene: MT-TG was added
gene: MT-TG was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-TG was set to MITOCHONDRIAL
Publications for gene: MT-TG were set to 8079988; 9199564; 11971101; 16120360; 32337339; 35432167; 10090480
Phenotypes for gene: MT-TG were set to Mitochondrial disease (MONDO:0044970), MT-TG-related
Review for gene: MT-TG was set to GREEN
Added comment: MODERATE by ClinGen.

Four variants reported in at least 6 individuals. Age of onset in affected individuals varied from early in life to the 20s. Clinical features included hypertrophic cardiomyopathy, myopathy, peripheral neuropathy, exercise intolerance, headache, seizures, ataxia, dystonic posturing, optic atrophy, retinal dystrophy, cataracts, and hearing loss. Progressive atrophy and bilateral basal ganglia calcifications were seen on brain imaging.

Tissue biopsies identified ragged red fibers and decreased COX histochemical activity in muscle. Lab values showed increased blood lactate and increased creatine kinase. Decreased activities of complexes I, III, and IV were observed in biopsied muscle.

Heteroplasmy levels of the variants in affected individuals ranged from 88-92% in muscle, 40-56% in urine, undetectable to 32% in blood, 27% in buccal samples, and was undetectable when assessed in fibroblasts. Single fiber testing and cybrid analysis further supported variant pathogenicity. This gene-disease relationship is also supported by known biochemical function and functional alterations in patient cells (in vitro functional assays demonstrated reduced rates of mitochondrial translation as a result of variants in MT-TG; PMID: 10090480).
Sources: Expert list
Mendeliome v1.3193 MT-TF Zornitza Stark edited their review of gene: MT-TF: Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TF-related
Mendeliome v1.3193 MT-TF Zornitza Stark Marked gene: MT-TF as ready
Mendeliome v1.3193 MT-TF Zornitza Stark Gene: mt-tf has been classified as Green List (High Evidence).
Mendeliome v1.3193 MT-TF Zornitza Stark Phenotypes for gene: MT-TF were changed from Mitochondrial disease (MONDO:0044970), MT-TF-relatedn to Mitochondrial disease (MONDO:0044970), MT-TF-related
Mendeliome v1.3192 MT-TF Zornitza Stark Classified gene: MT-TF as Green List (high evidence)
Mendeliome v1.3192 MT-TF Zornitza Stark Gene: mt-tf has been classified as Green List (High Evidence).
Mendeliome v1.3191 MT-TF Zornitza Stark Tag mtDNA tag was added to gene: MT-TF.
Mendeliome v1.3191 MT-TF Zornitza Stark gene: MT-TF was added
gene: MT-TF was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-TF was set to MITOCHONDRIAL
Publications for gene: MT-TF were set to 14659412; 9771776; 16806928; 21060018; 31463198; 32419253; 34607911; 21424749; 15184630; 20142618; 28267784; 31722346; 35472031; 9636664; 21882289; 16769874; 21914246; 31009750; 18977334
Phenotypes for gene: MT-TF were set to Mitochondrial disease (MONDO:0044970), MT-TF-relatedn
Review for gene: MT-TF was set to GREEN
Added comment: DEFINITIVE by ClinGen.

Over 30 individuals reported. Age of onset in affected individuals varied from childhood to >60 years. Clinical features in affected individuals included mitochondrial myopathy, MELAS, myoclonic epilepsy and ragged red fibers (MERRF), chronic external progressive ophthalmoplegia (CPEO), Gitelman syndrome, epilepsy, epilepsia partialis continua (EPC), chronic kidney disease, retinal dystrophy, sensorineural hearing loss, neuropathy, and neurologic/cognitive/psychiatric decline. Some affected individuals had normal brain imaging while others had cerebral, cerebellar, and/or brainstem atrophy.

Muscle biopsies showed ragged red fibers, COX-negative fibers, and decreased respiratory chain enzyme activities in some cases, although activities were normal in other individuals. Laboratory investigations showed variable lactate levels (normal to elevated in blood, cerebrospinal fluid, and/or urine) and elevated creatine kinase (CK).

Heteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed, and ranged from 58%-homoplasmic in muscle; 0-70% in hair, 0-homoplasmic in blood, fibroblast, and urine; and in one individual was 63% in a buccal sample.
Sources: Expert list
Mendeliome v1.3190 MT-TE Zornitza Stark Tag mtDNA tag was added to gene: MT-TE.
Mendeliome v1.3190 MT-TE Zornitza Stark Marked gene: MT-TE as ready
Mendeliome v1.3190 MT-TE Zornitza Stark Gene: mt-te has been classified as Green List (High Evidence).
Mendeliome v1.3190 MT-TE Zornitza Stark Classified gene: MT-TE as Green List (high evidence)
Mendeliome v1.3190 MT-TE Zornitza Stark Gene: mt-te has been classified as Green List (High Evidence).
Mendeliome v1.3189 MT-TE Zornitza Stark gene: MT-TE was added
gene: MT-TE was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-TE was set to MITOCHONDRIAL
Publications for gene: MT-TE were set to 8155739; 21194154; 17715279; 23334599; 7726155; 7726154; 9353617; 15048886; 15670724; 23847141; 23334599; 17266923; 17056256
Phenotypes for gene: MT-TE were set to Mitochondrial disease (MONDO:0044970), MT-TE-related
Review for gene: MT-TE was set to GREEN
Added comment: DEFINITIVE by ClinGen.

More than 15 individuals reported. Age of onset in affected individuals varied from birth to 30s. Clinical features in affected individuals included (benign) infantile reversible COX deficiency myopathy (also referred to RIRCD); chronic external progressive ophthalmoplegia (CPEO), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)/Leigh syndrome spectrum overlap, myoclonic epilepsy and ragged red fibers (MERRF); pigmentary retinopathy, migraines, myopathy, diabetes, pulmonary hypertension, ataxia, neuropathy, global developmental delay, dysarthria, and hearing loss. Brain imaging was variable. Muscle biopsies showed ragged red fibers, COX-negative fibers, and decreased respiratory chain enzyme activities in some cases, although activities were normal in other individuals.

Heteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed, and were variable in other tissues when tested.
Sources: Expert list
Mendeliome v1.3188 MT-TD Zornitza Stark Tag mtDNA tag was added to gene: MT-TD.
Mendeliome v1.3188 MT-TD Zornitza Stark Marked gene: MT-TD as ready
Mendeliome v1.3188 MT-TD Zornitza Stark Gene: mt-td has been classified as Green List (High Evidence).
Mendeliome v1.3188 MT-TD Zornitza Stark Classified gene: MT-TD as Green List (high evidence)
Mendeliome v1.3188 MT-TD Zornitza Stark Gene: mt-td has been classified as Green List (High Evidence).
Mendeliome v1.3187 MT-TD Zornitza Stark gene: MT-TD was added
gene: MT-TD was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-TD was set to MITOCHONDRIAL
Publications for gene: MT-TD were set to 9811342; 10488907; 16059939; 18676632; 23696415; 25447692; 27536005; 30030363; 3054486; 19535463
Phenotypes for gene: MT-TD were set to Mitochondrial disease (MONDO:0044970), MT-TD-related
Review for gene: MT-TD was set to GREEN
Added comment: MODERATE by ClinGen.

At least 3 variants reported in unrelated individuals. These variants were generally present at high levels of heteroplasmy in muscle tissue and at lower to undetectable levels in other tissues such as blood, saliva, buccal tissue, urine, and fibroblasts, highlighting the diagnostic importance of muscle biopsy in MT-TD-related primary mitochondrial disease. Single fiber studies were performed in several individuals with results supporting variant pathogenicity.

This gene-disease association is also supported by functional implication given protein interaction with the multitude of other mitochondrial translation proteins linked to primary mitochondrial disease (PMID: 30030363 ). Respiratory deficient yeast strains due to a single variant in MT-TD have been created and compelling rescue studies have been performed (PMIDs: 7024270, 3054486). E. coli carrying the m.7526A>G variant were also shown to have significantly decreased aminoacylation rates (PMID: 19535463).
Sources: Expert list
Mendeliome v1.3186 MT-TC Zornitza Stark Marked gene: MT-TC as ready
Mendeliome v1.3186 MT-TC Zornitza Stark Gene: mt-tc has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3186 MT-TC Zornitza Stark Classified gene: MT-TC as Amber List (moderate evidence)
Mendeliome v1.3186 MT-TC Zornitza Stark Gene: mt-tc has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3185 MT-TC Zornitza Stark gene: MT-TC was added
gene: MT-TC was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-TC was set to MITOCHONDRIAL
Publications for gene: MT-TC were set to 8829635; 9185178; 17241783; 11453453; 16955414; 32169613; 36039763; 17724295; 35252560; 34433719; 30030363
Phenotypes for gene: MT-TC were set to Mitochondrial disease (MONDO:0044970), MT-TC-related
Review for gene: MT-TC was set to AMBER
Added comment: LIMITED by ClinGen.

There were 3 scoreable probands across >10 publications from 1996-2022. Notably, while cybrid analyses were performed (PMID:36039763), one of the variants, m.5783G>A, was excluded from scoring for three reasons: 1.) the reported phenotype of isolated hearing loss was non-specific and incompletely penetrant, but also 2.) the biochemical impact in cybrids was mild - moderate, and 3.) there was reduction in expression of mitochondrial replication genes (TWNK ~30% of control in cybrids) suggesting an alternative aetiology might be responsible for the biochemical impact reported.

The gene-disease association for MT-TC is also supported by the known interaction with a multitude of other mitochondrial translation proteins (PMID:30030363) and respiratory chain studies and Northern blot analysis supporting MT-TC dysfunction leading to Complex I deficiency (PMID:35252560).
Sources: Expert list
Mendeliome v1.3184 NDP Sangavi Sivagnanasundram reviewed gene: NDP: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Norrie disease MONDO:0010691; Mode of inheritance: None
Mendeliome v1.3184 MT-TA Zornitza Stark Marked gene: MT-TA as ready
Mendeliome v1.3184 MT-TA Zornitza Stark Gene: mt-ta has been classified as Green List (High Evidence).
Mendeliome v1.3184 MT-TA Zornitza Stark Classified gene: MT-TA as Green List (high evidence)
Mendeliome v1.3184 MT-TA Zornitza Stark Gene: mt-ta has been classified as Green List (High Evidence).
Mendeliome v1.3183 MT-TA Zornitza Stark gene: MT-TA was added
gene: MT-TA was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-TA was set to MITOCHONDRIAL
Publications for gene: MT-TA were set to 11715067; 17825557; 14569122; 27014581; 20813205; 25873012; 16476954
Phenotypes for gene: MT-TA were set to Mitochondrial disease (MONDO:0044970), MT-TA-related
Review for gene: MT-TA was set to GREEN
Added comment: DEFINITIVE by ClinGen.

More than 5 individuals reported. Variable age of onset. Features in affected individuals included myopathy (weakness, exercise intolerance), ptosis, ophthalmoplegia, lipomas, and hearing loss. Muscle biopsies showed ragged red fibers and COX-negative fibers, as well as respiratory chain enzyme deficiencies. Heteroplasmy levels in affected individuals tended to be highest in muscle when multiple tissues were assessed and were variable in other tissues when tested.
Sources: Expert list
Mendeliome v1.3182 NDE1 Sangavi Sivagnanasundram reviewed gene: NDE1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly with lissencephaly and/or hydranencephaly, MONDO:0700116; Mode of inheritance: None
Mendeliome v1.3182 NARS Sangavi Sivagnanasundram reviewed gene: NARS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3182 NALCN Sangavi Sivagnanasundram reviewed gene: NALCN: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3182 NAGLU Sangavi Sivagnanasundram reviewed gene: NAGLU: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3182 NAA10 Sangavi Sivagnanasundram reviewed gene: NAA10: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: NAA10-related syndrome, MONDO:0100124; Mode of inheritance: None
Mendeliome v1.3182 MYRF Sangavi Sivagnanasundram reviewed gene: MYRF: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: MYRF-related cardiac-urogenital syndrome MONDO:0032653; Mode of inheritance: None
Mendeliome v1.3182 MYOT Sangavi Sivagnanasundram reviewed gene: MYOT: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: myofibrillar myopathy 3, MONDO:0012215; Mode of inheritance: None
Mendeliome v1.3182 PIP5K1C Sangavi Sivagnanasundram commented on gene: PIP5K1C
Mendeliome v1.3182 PITRM1 Sangavi Sivagnanasundram reviewed gene: PITRM1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: spinocerebellar ataxia, autosomal recessive 30, MONDO:0030318; Mode of inheritance: None
Mendeliome v1.3182 PJA1 Sangavi Sivagnanasundram reviewed gene: PJA1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: X-linked complex neurodevelopmental disorder, PJA1-related, MONDO:0100148; Mode of inheritance: None
Mendeliome v1.3182 MT-RNR1 Zornitza Stark Marked gene: MT-RNR1 as ready
Mendeliome v1.3182 MT-RNR1 Zornitza Stark Gene: mt-rnr1 has been classified as Green List (High Evidence).
Mendeliome v1.3182 MT-RNR1 Zornitza Stark Classified gene: MT-RNR1 as Green List (high evidence)
Mendeliome v1.3182 MT-RNR1 Zornitza Stark Gene: mt-rnr1 has been classified as Green List (High Evidence).
Mendeliome v1.3181 MT-RNR1 Zornitza Stark Tag mtDNA tag was added to gene: MT-RNR1.
Mendeliome v1.3181 MT-RNR1 Zornitza Stark gene: MT-RNR1 was added
gene: MT-RNR1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-RNR1 was set to MITOCHONDRIAL
Publications for gene: MT-RNR1 were set to 7698299; 16380089; 12920080; 24252789; 9490575; 8285309; 9040738; 7689389
Phenotypes for gene: MT-RNR1 were set to Mitochondrial disease (MONDO:0044970), MT-RNR1-related
Review for gene: MT-RNR1 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

Over 70 affected individuals reported. Two variants, m.1555A>G and m.1494C>T, are recurrent.

These variants are predominantly associated with hearing loss. Some individuals with this variants have normal hearing, others have hearing loss following aminoglycoside exposure, and others have hearing loss and no known aminoglycoside exposure. Age of onset of hearing loss ranged from infancy (after aminoglycoside exposure) to adulthood. Hearing loss has been reported to be variable, stable in some individuals and progressive in others.

Additional variants in this gene have been reported to be associated with primary mitochondrial disease, however insufficient clinical detail was provided and/or there was a lack of comprehensive analyses excluding other causes, therefore these additional variants were not included in the ClinGen curation (m.827A>G – PMIDs: 16650816, 16782057, 18261986; m.961delTinsC - PMIDs: 7550368, 10326749; m.1027A>G – PMIDs: 23328039, 21205314, 20100600; m.1095T>C – PMIDs: 11313749, 11079536, 15637703).
Sources: Expert list
Mendeliome v1.3180 MT-ND6 Zornitza Stark Marked gene: MT-ND6 as ready
Mendeliome v1.3180 MT-ND6 Zornitza Stark Gene: mt-nd6 has been classified as Green List (High Evidence).
Mendeliome v1.3180 MT-ND6 Zornitza Stark Classified gene: MT-ND6 as Green List (high evidence)
Mendeliome v1.3180 MT-ND6 Zornitza Stark Gene: mt-nd6 has been classified as Green List (High Evidence).
Mendeliome v1.3179 MT-ND6 Zornitza Stark gene: MT-ND6 was added
gene: MT-ND6 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-ND6.
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
Publications for gene: MT-ND6 were set to 5576045; 20019223; 21196529; 10894222; 14684687; 17535832; 19103152; 21749722; 23813926; 25356405; 14595656; 19062322; 11133798; 30741831; 21364701; 2018041
Phenotypes for gene: MT-ND6 were set to Mitochondrial disease (MONDO:0044970), MT-ND6-related
Review for gene: MT-ND6 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

More than 20 affected individuals reported, the m.14484T>C and m.14487T>C variants are recurrent.

Affected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and LSS phenotypes, as well as migraines, tremor, multiple sclerosis, and cardiac involvement. The age of onset is also highly variable, ranging from infantile to adult.

Muscle biopsies revealed isolated complex I deficiency, and complex I and III deficiencies; and complex I deficiency was also seen in fibroblasts and liver. Metabolic screening investigations showed elevated lactate and pyruvate in cerebrospinal fluid (CSF) and blood.

Heteroplasmy levels in affected individuals ranged from 50% to >95% in skeletal muscle; 25% to >95% in blood, 76% to >95% in fibroblasts, and 65% to >95% in liver; and ranged in healthy family members from undetectable to 92% in blood, undetectable to 95% in urine, 14% to 95% in hair follicles, 16% to 68% in buccal, and was undetectable in muscle in healthy family members.
Sources: Expert list
Mendeliome v1.3178 MT-ND5 Zornitza Stark Marked gene: MT-ND5 as ready
Mendeliome v1.3178 MT-ND5 Zornitza Stark Gene: mt-nd5 has been classified as Green List (High Evidence).
Mendeliome v1.3178 MT-ND5 Zornitza Stark Classified gene: MT-ND5 as Green List (high evidence)
Mendeliome v1.3178 MT-ND5 Zornitza Stark Gene: mt-nd5 has been classified as Green List (High Evidence).
Mendeliome v1.3177 MT-ND5 Zornitza Stark gene: MT-ND5 was added
gene: MT-ND5 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-ND5.
Mode of inheritance for gene gene: MT-ND5 was set to MITOCHONDRIAL
Publications for gene: MT-ND5 were set to 17400793; 11938446; 12624137; 18495510; 23918514; 17535832; 29506874; 23034978; 16816025; 9299505; 18977334
Phenotypes for gene: MT-ND5 were set to Mitochondrial disease (MONDO:0044970), MT-ND5-related
Review for gene: MT-ND5 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

More than 20 individuals reported. Two variants are recurrent (m.13513G>A and m.13094T>C).

Affected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); LSS; myoclonus epilepsy, ragged red fibers (MERRF); and cardiomyopathy. The age of onset is also highly variable, ranging from infantile to adult.

Muscle biopsies variably revealed ragged red fibers, isolated complex I deficiency, and variable combined deficiencies of complexes I, III, and/or IV. Metabolic screening investigations showed elevated lactate in cerebrospinal fluid (CSF) and blood and urinary excretion of Krebs cycle intermediates.

Heteroplasmy levels in affected individuals ranged from 28% - 90% in skeletal muscle, 23% to 77% in blood, undetectable to 90% in fibroblasts, 51% - 81% in urine; and ranged in healthy family members from undetectable to 20% in blood, undetectable to 25% to 95% in hair follicles, undetectable to 4-6% muscle, and ranged from 27%-45% in other tissues such as urine and buccal samples in healthy family members.
Sources: Expert list
Mendeliome v1.3176 MT-ND4L Zornitza Stark Marked gene: MT-ND4L as ready
Mendeliome v1.3176 MT-ND4L Zornitza Stark Gene: mt-nd4l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3176 MT-ND4L Zornitza Stark Classified gene: MT-ND4L as Amber List (moderate evidence)
Mendeliome v1.3176 MT-ND4L Zornitza Stark Gene: mt-nd4l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3175 MT-ND4L Zornitza Stark gene: MT-ND4L was added
gene: MT-ND4L was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-ND4L.
Mode of inheritance for gene gene: MT-ND4L was set to MITOCHONDRIAL
Publications for gene: MT-ND4L were set to 8680405; 11935318; 17003408; 22879922; 24568867
Phenotypes for gene: MT-ND4L were set to Mitochondrial disease (MONDO:0044970), MT-ND4L-related
Review for gene: MT-ND4L was set to AMBER
Added comment: LIMITED by ClinGen.

Seven probands with m.10063T>C have been reported across five publications, all of whom had LHON. These cases were scored with reduced points by ClinGen given the mild impact this variant has been shown to have on complex I function. While three other missense variants (m.10543A>G, m.10591T>G, m.10680G>A) have been reported, the ClinGen Expert Panel agreed there was only sufficient evidence of pathogenicity for the m.10663T>C variant. Cases with m.10680G>A and m.10543A>G and m.10591T>G were reviewed but excluded from scoring due to a lack of compelling functional evidence to support pathogenicity. The m.10543A>G variant has been modeled in E. coli and showed a very mild reduction in NADH dehydrogenase activity (74% of control), which was not sufficient to be included in scoring.
Sources: Expert list
Mendeliome v1.3174 MT-ND4 Zornitza Stark Marked gene: MT-ND4 as ready
Mendeliome v1.3174 MT-ND4 Zornitza Stark Gene: mt-nd4 has been classified as Green List (High Evidence).
Mendeliome v1.3174 MT-ND4 Zornitza Stark Classified gene: MT-ND4 as Green List (high evidence)
Mendeliome v1.3174 MT-ND4 Zornitza Stark Gene: mt-nd4 has been classified as Green List (High Evidence).
Mendeliome v1.3173 MT-ND4 Zornitza Stark gene: MT-ND4 was added
gene: MT-ND4 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-ND4.
Mode of inheritance for gene gene: MT-ND4 was set to MITOCHONDRIAL
Publications for gene: MT-ND4 were set to 12707444; 16120329; 15576045; 20502985; 27761019; 32445240; 32659360; 3201231
Phenotypes for gene: MT-ND4 were set to Mitochondrial disease (MONDO:0044970), MT-ND4-related
Review for gene: MT-ND4 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

Multiple individuals reported presenting with a broad phenotypic spectrum of clinical features including Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); LSS; cerebellar ataxia, migraines, regression, developmental delay, leukoencephalopathy, myoclonus, seizures, stroke-like episodes, cognitive decline, psychiatric illness, Parkinsonism, axonal neuropathy, multiple sclerosis, ophthalmoplegia, short stature, and hypertrophic cardiomyopathy. Age of onset varied from infancy to adulthood. Muscle biopsy showed COX-negative fibers and complex I deficiency.

Heteroplasmy levels in affected individuals ranged from 60% - 83% in muscle, 40% - 80% in blood, and 76% - 78% in myoblasts, as well as from 57% - 73% in various other tissues (fibroblasts, liver, urine, buccal). Of note, the m.11778G>A common LHON variant was reported in affected individuals in the homoplasmic and heteroplasmic states.
Sources: Expert list
Mendeliome v1.3172 MT-ND3 Zornitza Stark Marked gene: MT-ND3 as ready
Mendeliome v1.3172 MT-ND3 Zornitza Stark Gene: mt-nd3 has been classified as Green List (High Evidence).
Mendeliome v1.3172 MT-ND3 Zornitza Stark Classified gene: MT-ND3 as Green List (high evidence)
Mendeliome v1.3172 MT-ND3 Zornitza Stark Gene: mt-nd3 has been classified as Green List (High Evidence).
Mendeliome v1.3171 MT-ND3 Zornitza Stark gene: MT-ND3 was added
gene: MT-ND3 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-ND3.
Mode of inheritance for gene gene: MT-ND3 was set to MITOCHONDRIAL
Publications for gene: MT-ND3 were set to 1928099; 14705112; 14764913; 17152068; 20202874; 25118196; 25384404; 11456298; 19458970; 30199507; 29237403
Phenotypes for gene: MT-ND3 were set to Mitochondrial disease (MONDO:0044970), MT-ND3-related
Review for gene: MT-ND3 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

More than 15 affected individuals reported. Three variants are recurrent (m.10158T>C, m.10191T>C, m.10197G>A). Affected individuals present with a broad phenotypic spectrum of clinical features including LSS; Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); lactic acidosis, epilepsia partialis continua (EPC), epileptic encephalopathy, dystonia, and optic atrophy. The age of onset is also highly variable, ranging from infantile to adult. Muscle biopsy showed and complex I deficiency.
Sources: Expert list
Mendeliome v1.3170 MT-ND2 Zornitza Stark Marked gene: MT-ND2 as ready
Mendeliome v1.3170 MT-ND2 Zornitza Stark Gene: mt-nd2 has been classified as Green List (High Evidence).
Mendeliome v1.3170 MT-ND2 Zornitza Stark Classified gene: MT-ND2 as Green List (high evidence)
Mendeliome v1.3170 MT-ND2 Zornitza Stark Gene: mt-nd2 has been classified as Green List (High Evidence).
Mendeliome v1.3169 MT-ND2 Zornitza Stark gene: MT-ND2 was added
gene: MT-ND2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-ND2 was set to MITOCHONDRIAL
Publications for gene: MT-ND2 were set to 26258512; 16738010; 15781840; 12192017
Phenotypes for gene: MT-ND2 were set to Mitochondrial disease (MONDO:0044970), MT-ND2-related
Review for gene: MT-ND2 was set to GREEN
Added comment: MODERATE by ClinGen.

Multiple individuals reported. Age of onset in affected individuals ranged from 9 months old to childhood. Clinical features in affected individuals included Leigh syndrome spectrum, myopathy, ophthalmoplegia, and ptosis. Muscle biopsies revealed ragged red fibers and complex I deficiency. Metabolic screening labs showed elevated lactate and creatine kinase (CK). Heteroplasmy levels were >95% in blood, fibroblasts, and muscle in the individual with Leigh syndrome spectrum. However in the other two individuals with predominantly myopathic features, the variant was present at >94% in muscle and undetectable in other tissues tested.
Sources: Expert list
Mendeliome v1.3168 MT-ND1 Zornitza Stark Marked gene: MT-ND1 as ready
Mendeliome v1.3168 MT-ND1 Zornitza Stark Gene: mt-nd1 has been classified as Green List (High Evidence).
Mendeliome v1.3168 MT-ND1 Zornitza Stark Classified gene: MT-ND1 as Green List (high evidence)
Mendeliome v1.3168 MT-ND1 Zornitza Stark Gene: mt-nd1 has been classified as Green List (High Evidence).
Mendeliome v1.3167 MT-ND1 Zornitza Stark gene: MT-ND1 was added
gene: MT-ND1 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-ND1.
Mode of inheritance for gene gene: MT-ND1 was set to MITOCHONDRIAL
Publications for gene: MT-ND1 were set to 39147111; 36717040; 34656796
Phenotypes for gene: MT-ND1 were set to Mitochondrial respiratory chain complex deficiency, MONDO:0000066, MT-ND1-related
Review for gene: MT-ND1 was set to GREEN
Added comment: Multiple individuals reported with variants in this gene and a range of phenotypes consistent with mitochondrial disease, including LHON and Leigh syndrome.
Sources: Expert list
Mendeliome v1.3166 MT-CYB Zornitza Stark changed review comment from: Multiple individuals reported with variants in this gene and a range of clinical phenotypes consistent with mitochondrial disease.
Sources: Expert list; to: Multiple individuals reported with variants in this gene and a range of clinical phenotypes consistent with mitochondrial disease, including Leber's optic atrophy, encephalomyopathy, and cardiomyopathy.
Sources: Expert list
Mendeliome v1.3166 MT-CYB Zornitza Stark Marked gene: MT-CYB as ready
Mendeliome v1.3166 MT-CYB Zornitza Stark Gene: mt-cyb has been classified as Green List (High Evidence).
Mendeliome v1.3166 MT-CYB Zornitza Stark Classified gene: MT-CYB as Green List (high evidence)
Mendeliome v1.3166 MT-CYB Zornitza Stark Gene: mt-cyb has been classified as Green List (High Evidence).
Mendeliome v1.3165 MT-CYB Zornitza Stark gene: MT-CYB was added
gene: MT-CYB was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-CYB.
Mode of inheritance for gene gene: MT-CYB was set to MITOCHONDRIAL
Publications for gene: MT-CYB were set to 39858655; 34804306; 26937408
Phenotypes for gene: MT-CYB were set to mitochondrial respiratory chain complex deficiency, MONDO:0000066, MT-CYB-related
Review for gene: MT-CYB was set to GREEN
Added comment: Multiple individuals reported with variants in this gene and a range of clinical phenotypes consistent with mitochondrial disease.
Sources: Expert list
Mendeliome v1.3163 MT-CO2 Zornitza Stark Marked gene: MT-CO2 as ready
Mendeliome v1.3163 MT-CO2 Zornitza Stark Gene: mt-co2 has been classified as Green List (High Evidence).
Mendeliome v1.3163 MT-CO2 Zornitza Stark Classified gene: MT-CO2 as Green List (high evidence)
Mendeliome v1.3163 MT-CO2 Zornitza Stark Gene: mt-co2 has been classified as Green List (High Evidence).
Mendeliome v1.3162 MT-CO2 Zornitza Stark gene: MT-CO2 was added
gene: MT-CO2 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-CO2.
Mode of inheritance for gene gene: MT-CO2 was set to MITOCHONDRIAL
Publications for gene: MT-CO2 were set to 37640115; 34325999; 30315213; 28521807
Phenotypes for gene: MT-CO2 were set to Mitochondrial respiratory chain complex deficiency, MONDO:0000066, MT-CO2-related
Review for gene: MT-CO2 was set to GREEN
Added comment: Multiple individuals reported with variants in this gene and a range of neurological and neuromuscular presentations consistent with mitochondrial disease.
Sources: Expert list
Mendeliome v1.3161 MT-CO1 Zornitza Stark Marked gene: MT-CO1 as ready
Mendeliome v1.3161 MT-CO1 Zornitza Stark Gene: mt-co1 has been classified as Green List (High Evidence).
Mendeliome v1.3161 MT-CO1 Zornitza Stark Classified gene: MT-CO1 as Green List (high evidence)
Mendeliome v1.3161 MT-CO1 Zornitza Stark Gene: mt-co1 has been classified as Green List (High Evidence).
Mendeliome v1.3160 MT-CO1 Zornitza Stark Tag mtDNA tag was added to gene: MT-CO1.
Mendeliome v1.3160 MT-CO1 Zornitza Stark gene: MT-CO1 was added
gene: MT-CO1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene gene: MT-CO1 was set to MITOCHONDRIAL
Publications for gene: MT-CO1 were set to 30743023; 39460813; 24956508
Phenotypes for gene: MT-CO1 were set to Mitochondrial respiratory chain complex deficiency, MONDO:0000066, MT-CO1-related
Review for gene: MT-CO1 was set to GREEN
Added comment: Multiple individuals reported with a range of clinical presentations consistent with mitochondrial disease.
Sources: Expert list
Mendeliome v1.3159 MT-ATP8 Zornitza Stark Marked gene: MT-ATP8 as ready
Mendeliome v1.3159 MT-ATP8 Zornitza Stark Gene: mt-atp8 has been classified as Green List (High Evidence).
Mendeliome v1.3159 MT-ATP8 Zornitza Stark Classified gene: MT-ATP8 as Green List (high evidence)
Mendeliome v1.3159 MT-ATP8 Zornitza Stark Gene: mt-atp8 has been classified as Green List (High Evidence).
Mendeliome v1.3158 MT-ATP8 Zornitza Stark gene: MT-ATP8 was added
gene: MT-ATP8 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-ATP8.
Mode of inheritance for gene gene: MT-ATP8 was set to MITOCHONDRIAL
Publications for gene: MT-ATP8 were set to 40112238
Phenotypes for gene: MT-ATP8 were set to Mitochondrial complex V (ATP synthase) deficiency, MONDO:0014471, MT-ATP8-related
Review for gene: MT-ATP8 was set to GREEN
Added comment: Multiple individuals reported with wide spectrum of clinical features including ataxia, motor and language developmental delay, deafness, retinitis pigmentosa, and Leigh pattern in brain MRI.
Sources: Expert list
Mendeliome v1.3157 MT-ATP6 Zornitza Stark Marked gene: MT-ATP6 as ready
Mendeliome v1.3157 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Green List (High Evidence).
Mendeliome v1.3157 MT-ATP6 Zornitza Stark Classified gene: MT-ATP6 as Green List (high evidence)
Mendeliome v1.3157 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Green List (High Evidence).
Mendeliome v1.3156 MT-ATP6 Zornitza Stark gene: MT-ATP6 was added
gene: MT-ATP6 was added to Mendeliome. Sources: Expert list
mtDNA tags were added to gene: MT-ATP6.
Mode of inheritance for gene gene: MT-ATP6 was set to MITOCHONDRIAL
Publications for gene: MT-ATP6 were set to 40112238
Phenotypes for gene: MT-ATP6 were set to Mitochondrial complex V (ATP synthase) deficiency, MONDO:0014471, MT-ATP6-related
Review for gene: MT-ATP6 was set to GREEN
Added comment: Multiple individuals reported with wide spectrum of clinical features including ataxia, motor and language developmental delay, deafness, retinitis pigmentosa, and Leigh pattern in brain MRI.
Sources: Expert list
Mendeliome v1.3155 BRSK2 Zornitza Stark Phenotypes for gene: BRSK2 were changed from Intellectual disability; autism to Neurodevelopmental disorder, MONDO:0700092, BRSK2-related
Mendeliome v1.3154 BRSK2 Zornitza Stark edited their review of gene: BRSK2: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, BRSK2-related
Mendeliome v1.3154 BMP7 Zornitza Stark Phenotypes for gene: BMP7 were changed from Non-syndromic metopic craniosynostosis; Congenital abnormalities of the kidneys and urinary tract; Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) to Congenital anomaly of kidney and urinary tract, MONDO:0019719, BMP7-related; Isolated craniosynostosis, MONDO:0015337, BMP7-related; Mayer-Rokitansky-Kuster-Hauser syndrome, MONDO:0017771, BMP7-related
Mendeliome v1.3153 BMP7 Sarah Milton reviewed gene: BMP7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital anomaly of kidney and urinary tract, MONDO:0019719, BMP7-related, Isolated craniosynostosis, MONDO:0015337, BMP7-related, Mayer-Rokitansky-Kuster-Hauser syndrome, MONDO:0017771, BMP7-related; Mode of inheritance: None
Mendeliome v1.3153 TBX2 Zornitza Stark reviewed gene: TBX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 20206336, 22052739, 21271665, https://doi.org/10.1101/2024.07.18.24310488; Phenotypes: Hearing loss disorder, MONDO:0005365, TBX2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3153 NTN1 Zornitza Stark Phenotypes for gene: NTN1 were changed from Mirror movements 4 MIM#618264 to Mirror movements 4 MIM#618264; Hearing loss disorder, MONDO:0005365, NTN1-related
Mendeliome v1.3152 NTN1 Zornitza Stark Publications for gene: NTN1 were set to 25763452; 28945198; 33472083
Mendeliome v1.3151 NTN1 Zornitza Stark reviewed gene: NTN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39648562; Phenotypes: Hearing loss disorder, MONDO:0005365, NTN1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3151 GNAI2 Zornitza Stark Phenotypes for gene: GNAI2 were changed from Pituitary adenoma, ACTH-secreting, somatic; Ventricular tachycardia, idiopathic 192605; Syndromic developmental disorder to Syndromic disease MONDO:0002254, GNAI2-related
Mendeliome v1.3150 GNAI2 Zornitza Stark Publications for gene: GNAI2 were set to PMID: 31036916
Mendeliome v1.3149 GNAI2 Zornitza Stark Classified gene: GNAI2 as Green List (high evidence)
Mendeliome v1.3149 GNAI2 Zornitza Stark Gene: gnai2 has been classified as Green List (High Evidence).
Mendeliome v1.3148 TRPC5 Zornitza Stark Publications for gene: TRPC5 were set to PMID: 36323681; 24817631; 23033978; 33504798; 28191890
Mendeliome v1.3147 BMPR1A Zornitza Stark Phenotypes for gene: BMPR1A were changed from Polyposis, juvenile intestinal, MIM# 174900 to BMPR1A-related juvenile polyposis syndrome MONDO:0700348
Mendeliome v1.3146 CDK5 Zornitza Stark Publications for gene: CDK5 were set to 25560765; 32273484; 32097629; 28854363; 7490100
Mendeliome v1.3145 CDK5 Zornitza Stark Classified gene: CDK5 as Green List (high evidence)
Mendeliome v1.3145 CDK5 Zornitza Stark Gene: cdk5 has been classified as Green List (High Evidence).
Mendeliome v1.3144 PACSIN3 Zornitza Stark Phenotypes for gene: PACSIN3 were changed from Myopathy, MONDO:0005336, PACSIN3-related to Congenital myopathy 27, MIM# 621343
Mendeliome v1.3143 PACSIN3 Zornitza Stark edited their review of gene: PACSIN3: Changed phenotypes: Congenital myopathy 27, MIM# 621343
Mendeliome v1.3143 GNAI2 Rylee Peters reviewed gene: GNAI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 40926810, 39298586; Phenotypes: Syndromic disease MONDO:0002254, GNAI2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3143 TRPC5 Rylee Peters reviewed gene: TRPC5: Rating: AMBER; Mode of pathogenicity: None; Publications: 40907672; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, TRPC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3143 BMPR1A Leah Frajman reviewed gene: BMPR1A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: BMPR1A-related juvenile polyposis syndrome MONDO:0700348; Mode of inheritance: None
Mendeliome v1.3143 PRKCI Sangavi Sivagnanasundram edited their review of gene: PRKCI: Changed rating: GREEN
Mendeliome v1.3143 PRKCI Sangavi Sivagnanasundram changed review comment from: Multiple reported variants in affected individuals mainly presenting with lower lip pits and orofacial clefts (OFCs). Some individuals presented with a more severe phenotype inclusing seizures, ID/DD and urogenital anomalies. Supportive zebrafish model supporting a loss-of-function mechanism was performed on three recurrent variants [c.389G>A (p.Arg130His), c.1148A>G (p.Asn383Ser), and c.1155A>C (p.Leu385Phe)] however there is not enough evidence to show that LoF is the mechanism of disease.

The gene is not constrained for LoF in gnomAD and there are no pathogenic SNVs reported in ClinVar at this present time. Amber until further evidence is published in support of this gene-disease association.
Sources: Literature; to: Multiple reported variants in affected individuals mainly presenting with lower lip pits and orofacial clefts (OFCs). Some individuals presented with a more severe phenotype inclusing seizures, ID/DD and urogenital anomalies. Supportive zebrafish model supporting a loss-of-function mechanism was performed on three recurrent variants [c.389G>A (p.Arg130His), c.1148A>G (p.Asn383Ser), and c.1155A>C (p.Leu385Phe)] however there is not enough evidence to show that LoF is the mechanism of disease.

Sources: Literature
Mendeliome v1.3143 CDK5 Arina Puzriakova reviewed gene: CDK5: Rating: GREEN; Mode of pathogenicity: None; Publications: 40186457; Phenotypes: Lissencephaly 7 with cerebellar hypoplasia, OMIM:616342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3143 ANLN Zornitza Stark Publications for gene: ANLN were set to 24676636; 30002222
Mendeliome v1.3142 ANLN Zornitza Stark edited their review of gene: ANLN: Added comment: Further reports but evidence is conflicting, including variants with implausibly high pop frequency.

Gbadegesin et al (2014); Hall et al (2018) 2 x families reported with FSGS (USA) and missense variants G618C (v4: absent) and R431C (v4: 63 hets, 0 hom). R431C was identified in 6 affected family members and absent in 6 unaffected family members. G618C was present in the proband and absent in 4 unaffected family members, the other 2 affected individuals from this family were not genotyped (deceased). Missense demostrated as LoF with both in vitro and in vivo (zebrafish). R431C was shown to disrupt interaction with CD2AP (primarily LoF effect), causing downstream hyperactivation of the PI3K/AKT/mTOR/Rac1 signaling pathway, which drives podocytes hypermotility.

Geminiganesan et al (2021) 1 x 2 year old child (India) with early-onset steroid resistant nephrotic syndrome, whole-exome sequencing and genome-wide linkage studies, a missense variant in ANLN was identified p.Thr821Met (v4: 508 hets, 0 hom).

Zhang et al (2023) 3 x children with steroid resistant nephrotic syndrome (China). 2 x missense (p.M1099I - LP (v4:1 het, 0 hom), p.S140T - VUS (v4: 6 hets, 0 hom) and 1 x stop gain reported p.R39X - LP ( v4: 1 het, 0 hom).

Lin et al (2023) 3 x unrelated individuals with missense E841K (China, v4: 618 hets, 2 hom). In famly A the variant was de novo, in family 2 only the proband as tested, in family 3 the variant was inherited from an affected father. 4 x unaffected individuals did not have the variant. Knockout mouse model inconclusive, did not show any effect until 36 weeks. Zebrafish model was also inconclusive.; Changed publications: 24676636, 30002222, 34819827, 38322629, 37957688
Mendeliome v1.3142 COL4A3BP Zornitza Stark Phenotypes for gene: COL4A3BP were changed from Intellectual developmental disorder 34 (MIM#616351) to Neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic facies (MIM#616351)
Mendeliome v1.3141 COL4A3BP Zornitza Stark edited their review of gene: COL4A3BP: Changed phenotypes: Neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic facies (MIM#616351)
Mendeliome v1.3141 COL4A3BP Zornitza Stark Phenotypes for gene: COL4A3BP were changed from Neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic facies (MIM#616351) to Intellectual developmental disorder 34 (MIM#616351)
Mendeliome v1.3140 PRKCI Zornitza Stark Marked gene: PRKCI as ready
Mendeliome v1.3140 PRKCI Zornitza Stark Gene: prkci has been classified as Green List (High Evidence).