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Mendeliome v1.538 CHUK Zornitza Stark edited their review of gene: CHUK: Added comment: PMID 34533979: single individual reported with homozygous missense variant in this gene and recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine. Supportive functional data.; Changed publications: 25691407, 20961246, 10195895, 10195896, 29523099, 28513979, 34533979
Mendeliome v1.537 IRF7 Zornitza Stark Classified gene: IRF7 as Green List (high evidence)
Mendeliome v1.537 IRF7 Zornitza Stark Gene: irf7 has been classified as Green List (High Evidence).
Mendeliome v1.536 IRF7 Zornitza Stark Classified gene: IRF7 as Green List (high evidence)
Mendeliome v1.536 IRF7 Zornitza Stark Gene: irf7 has been classified as Green List (High Evidence).
Mendeliome v1.535 LIG1 Zornitza Stark Phenotypes for gene: LIG1 were changed from Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis to Immunodeficiency 96, MIM# 619774; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis
Mendeliome v1.534 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Amber List (Moderate Evidence).
Mendeliome v1.533 NLGN4X Zornitza Stark Classified gene: NLGN4X as Amber List (moderate evidence)
Mendeliome v1.533 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Amber List (Moderate Evidence).
Mendeliome v1.532 TIMMDC1 Zornitza Stark Classified gene: TIMMDC1 as Green List (high evidence)
Mendeliome v1.532 TIMMDC1 Zornitza Stark Gene: timmdc1 has been classified as Green List (High Evidence).
Mendeliome v1.531 MPC2 Zornitza Stark Gene: mpc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.531 MPC2 Zornitza Stark Classified gene: MPC2 as Amber List (moderate evidence)
Mendeliome v1.531 MPC2 Zornitza Stark Gene: mpc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.530 MPC2 Zornitza Stark gene: MPC2 was added
gene: MPC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPC2 were set to 36417180
Phenotypes for gene: MPC2 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related
Review for gene: MPC2 was set to AMBER
Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels.
Sources: Literature
Mendeliome v1.527 ARF3 Zornitza Stark Classified gene: ARF3 as Green List (high evidence)
Mendeliome v1.527 ARF3 Zornitza Stark Gene: arf3 has been classified as Green List (High Evidence).
Mendeliome v1.523 NUP54 Zornitza Stark Gene: nup54 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.523 NUP54 Zornitza Stark Phenotypes for gene: NUP54 were changed from Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Mendeliome v1.521 UQCRH Zornitza Stark Classified gene: UQCRH as Amber List (moderate evidence)
Mendeliome v1.521 UQCRH Zornitza Stark Gene: uqcrh has been classified as Amber List (Moderate Evidence).
Mendeliome v1.520 FEM1C Zornitza Stark Gene: fem1c has been classified as Green List (High Evidence).
Mendeliome v1.520 FEM1C Zornitza Stark Classified gene: FEM1C as Green List (high evidence)
Mendeliome v1.520 FEM1C Zornitza Stark Gene: fem1c has been classified as Green List (High Evidence).
Mendeliome v1.519 DCLRE1B Zornitza Stark Phenotypes for gene: DCLRE1B were changed from Dyskeratosis congenita and Hoyeraal-Hreidarsson (HH) syndrome to Dyskeratosis congenita, autosomal recessive 8, MIM# 620133
Mendeliome v1.516 DCLRE1B Zornitza Stark Classified gene: DCLRE1B as Green List (high evidence)
Mendeliome v1.516 DCLRE1B Zornitza Stark Gene: dclre1b has been classified as Green List (High Evidence).
Mendeliome v1.514 NUP54 Zornitza Stark Classified gene: NUP54 as Amber List (moderate evidence)
Mendeliome v1.514 NUP54 Zornitza Stark Gene: nup54 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.513 NUP54 Hazel Phillimore gene: NUP54 was added
gene: NUP54 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP54 were set to PMID: 36333996
Phenotypes for gene: NUP54 were set to Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Mode of pathogenicity for gene: NUP54 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: NUP54 was set to AMBER
Added comment: From PMID: 36333996.; Harrer, P. et al. (2022) Ann Neurol. doi: 10.1002/ana.26544.

Three patients from unrelated families with dystonia and/or Leigh(-like) syndromes, with biallelic variants in NUP54, in the C-terminal protein region that interacts with NUP62. Onset was between 12 months and 5 years. All had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

Patient / Family A (consanguineous) was homozygous for c.1073T>G p.(Ile358Ser).

Patient / Family B was compound heterozygous for c.1073T>G p.(Ile358Ser) and c.1126A>G p.(Lys376Glu).

Patient / Family C was compound heterozygosity for c.1410_1412del p.(Gln471del) and two missense variants c.1414G>A, p.(Glu472Lys); c.1420C>T, p.(Leu474Phe)

The phenotypes were similar to those of NUP62 including early-onset dystonia with dysphagic choreoathetosis, and T2-hyperintense lesions in striatum.

Brain MRIs showed T2/FLAIR hyperintensities in the dorsal putamina.

Western blots showing reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts.
Sources: Literature
Mendeliome v1.513 GABRA3 Zornitza Stark Gene: gabra3 has been classified as Green List (High Evidence).
Mendeliome v1.512 GABRA3 Zornitza Stark Classified gene: GABRA3 as Green List (high evidence)
Mendeliome v1.512 GABRA3 Zornitza Stark Gene: gabra3 has been classified as Green List (High Evidence).
Mendeliome v1.511 DCLRE1B Manny Jacobs reviewed gene: DCLRE1B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 10699141, 20479256, 35007328; Phenotypes: Dyskeratosis congenita, autosomal recessive 8; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.511 NPC1 Naomi Baker gene: NPC1 was added
gene: NPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 36417180
Phenotypes for gene: NPC1 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related
Review for gene: NPC1 was set to AMBER
Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels.
Sources: Literature
Mendeliome v1.508 EMILIN1 Zornitza Stark Classified gene: EMILIN1 as Green List (high evidence)
Mendeliome v1.508 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Green List (High Evidence).
Mendeliome v1.507 GABRA3 Sarah Pantaleo gene: GABRA3 was added
gene: GABRA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GABRA3 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: GABRA3 were set to PMID: 29053855
Phenotypes for gene: GABRA3 were set to Epilepsy, intellectual disability, dysmorphic features,
Penetrance for gene: GABRA3 were set to Incomplete
Review for gene: GABRA3 was set to GREEN
Added comment: Six variants in GABRA3 encoding the alpha3-subunit of the GABA(A) receptor.
Five missense variants and one micro duplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus.
The variants co-segregated mostly but not completely with the phenotype in the families, indicating in some cases incomplete penetrance, involvement of other genes, or presence of phenocopies.
Overall, males were more severely affected and there were three asymptomatic female mutation carriers compared to only one male without a clinical phenotype.
Mechanism suggested - three detected missense variants are localised in the extracellular GABA-binding NH2-terminus, one in the M2-M3 linker and one in the M4 transmembrane segment of the alpha3-subunit. Functional studies in Xenopus leaves oocytes revealed a variable but significant reduction of GABA-evoked anion currents for all mutants compared to wild-type receptors. The degree of current reduction correlated partially with the phenotype.
Results reveal that rare loss-of-function variants in GABRA3 increase the risk for a varying combination of epilepsy, intellectual disability/developmental delay and dysmorphic features, presenting in some pedigrees with an X-linked inheritance pattern.
Sources: Literature
Mendeliome v1.507 TCEAL1 Zornitza Stark Gene: tceal1 has been classified as Green List (High Evidence).
Mendeliome v1.506 TCEAL1 Zornitza Stark Classified gene: TCEAL1 as Green List (high evidence)
Mendeliome v1.506 TCEAL1 Zornitza Stark Gene: tceal1 has been classified as Green List (High Evidence).
Mendeliome v1.505 TCEAL1 Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature
Mendeliome v1.505 SHROOM4 Alison Yeung Classified gene: SHROOM4 as Green List (high evidence)
Mendeliome v1.505 SHROOM4 Alison Yeung Gene: shroom4 has been classified as Green List (High Evidence).
Mendeliome v1.504 TCEAL1 Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature
Mendeliome v1.504 TCEAL1 Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature
Mendeliome v1.504 UQCRH Chern Lim gene: UQCRH was added
gene: UQCRH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UQCRH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UQCRH were set to 34750991
Phenotypes for gene: UQCRH were set to Mitochondrial complex III deficiency, nuclear type 11, MIM#620137
Review for gene: UQCRH was set to AMBER
gene: UQCRH was marked as current diagnostic
Added comment: PMID: 34750991:
- Two affected cousins, presented with recurrent episodes of severe lactic acidosis, hyperammonaemia, hypoglycaemia and encephalopathy.
- Both have a 2.2 kb homozygous deletion of exons 2 and 3 of UQCRH, predicted to culminate in an in-frame deletion exons 2 and 3 of the four-exon UQCRH gene, resulting in a shortened product.
- Mouse model with the equivalent homozygous Uqcrh deletion (Uqcrh-/-) also presented with lactic acidosis and hyperammonaemia, but had a more severe, non-episodic phenotype, resulting in failure to thrive and early death.
- Patient fibroblasts and Uqcrh-/- mouse tissues showed a CIII defect.
- Expression of wild-type UQCRH in patient fibroblasts ameliorates the CIII defect.
Sources: Literature
Mendeliome v1.504 FEM1C Paul De Fazio gene: FEM1C was added
gene: FEM1C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FEM1C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FEM1C were set to 36336956; 28135719; 33398170; 33398168
Phenotypes for gene: FEM1C were set to Neurodevelopmental disorder, FEM1C-related MONDO:0700092
Review for gene: FEM1C was set to GREEN
gene: FEM1C was marked as current diagnostic
Added comment: PMID:36336956 describes a 9-year-old boy with severe DD, lack of speech, pyramidal signs, and limb ataxia who had a de novo missense variant Asp126His in FEM1C ascertained by WES. The equivalent variant introduced into the nematode C.elegans resulted in disabled locomotion caused by synaptic abnormalities and not muscle dysfunction.

An alternate change Asp126Val was reported in the DDD study de novo in a patient with uncharacterised developmental delay (PMID:28135719).

The Asp126 residue (but not either of the variants above specifically) was shown to be functionally important by in vitro studies (PMID:33398170;33398168). The residue is highly conserved and located in a region of missense constraint.

Borderline green, 2 patients and an animal model. Note all evidence points to the Asp126 residue being of specific importance.
Sources: Literature
Mendeliome v1.504 TCEAL1 Melanie Marty gene: TCEAL1 was added
gene: TCEAL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TCEAL1 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: TCEAL1 were set to PMID: 36368327
Phenotypes for gene: TCEAL1 were set to hypotonia, abnormal gait, developmental delay, intellectual disability, autism, dysmorphic facial features.
Review for gene: TCEAL1 was set to GREEN
Added comment: 7 individuals (males and females) with de novo variants involving TCEAL1. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature
Mendeliome v1.504 KDM2B Ain Roesley changed review comment from: 27 individuals from 22 families were recruited
12 SNV classified LP/P, all de novo except 2 familial cases
5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function)
Sources: Literature; to: 27 individuals from 22 families were recruited
13 SNV classified LP/P, all de novo except 2 familial cases
5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function)
Sources: Literature
Mendeliome v1.504 KDM2B Ain Roesley Gene: kdm2b has been classified as Green List (High Evidence).
Mendeliome v1.504 KDM2B Ain Roesley Classified gene: KDM2B as Green List (high evidence)
Mendeliome v1.504 KDM2B Ain Roesley Gene: kdm2b has been classified as Green List (High Evidence).
Mendeliome v1.503 MAN2A2 Zornitza Stark Gene: man2a2 has been classified as Red List (Low Evidence).
Mendeliome v1.503 KDM2B Ain Roesley gene: KDM2B was added
gene: KDM2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM2B were set to 36322151
Phenotypes for gene: KDM2B were set to neurodevelopmental disorder MONDO#070009, KDM2B-related
Review for gene: KDM2B was set to GREEN
gene: KDM2B was marked as current diagnostic
Added comment: 27 individuals from 22 families were recruited
12 SNV classified LP/P, all de novo except 2 familial cases
5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function)
Sources: Literature
Mendeliome v1.502 MAN2A2 Zornitza Stark gene: MAN2A2 was added
gene: MAN2A2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAN2A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2A2 were set to 36357165
Phenotypes for gene: MAN2A2 were set to Congenital disorder of glycosylation, MONDO:0015286, MAN2A2-reated
Review for gene: MAN2A2 was set to RED
Added comment: Single consanguineous family reported with homozygous truncating variant in two brothers with ID. Supportive biochemical data only.
Sources: Literature
Mendeliome v1.500 MLIP Zornitza Stark Phenotypes for gene: MLIP were changed from MLIP-related myopathy with rhabdomyolysis to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138
Mendeliome v1.499 MLIP Zornitza Stark reviewed gene: MLIP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.499 UBE3C Zornitza Stark Gene: ube3c has been classified as Green List (High Evidence).
Mendeliome v1.498 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Mendeliome v1.496 UBE3C Chirag Patel Classified gene: UBE3C as Green List (high evidence)
Mendeliome v1.496 UBE3C Chirag Patel Gene: ube3c has been classified as Green List (High Evidence).
Mendeliome v1.494 HECTD4 Chirag Patel Classified gene: HECTD4 as Green List (high evidence)
Mendeliome v1.494 HECTD4 Chirag Patel Gene: hectd4 has been classified as Green List (High Evidence).
Mendeliome v1.492 KIF26A Chirag Patel Classified gene: KIF26A as Green List (high evidence)
Mendeliome v1.492 KIF26A Chirag Patel Gene: kif26a has been classified as Green List (High Evidence).
Mendeliome v1.491 KIF26A Chirag Patel gene: KIF26A was added
gene: KIF26A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF26A were set to PMID: 36228617
Phenotypes for gene: KIF26A were set to Congenital brain malformations, no OMIM #
Review for gene: KIF26A was set to GREEN
Added comment: 5 unrelated patients with biallelic loss-of-function variants in KIF26A (found through WES), exhibiting a spectrum of congenital brain malformations (schizencephaly, corpus callosum anomalies, polymicrgyria, and ventriculomegaly). Combining mice and human iPSC-derived organoid models, they discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and axonal growth, and apoptosis, offering a convincing explanation of the disease etiology in patients. Single-cell RNA sequencing in KIF26A knockout organoids revealed transcriptional changes in MAPK, MYC, and E2F pathways.
Sources: Literature
Mendeliome v1.490 TAMM41 Zornitza Stark Phenotypes for gene: TAMM41 were changed from inborn mitochondrial metabolism disorder MONDO:0004069; hypotonia; developmental delay; myopathy; ptosis to Combined oxidative phosphorylation deficiency-56 (COXPD56), MIM#620139; hypotonia; developmental delay; myopathy; ptosis
Mendeliome v1.489 PIGN Zornitza Stark edited their review of gene: PIGN: Added comment: Large cohort study of 21 new and review of 40 previously published cases in PMID 36322149

Biallelic-truncating variants were detected in 16 patients-10 with Fryns syndrome, 1 with MCAHS1, 2 with Fryns syndrome/MCAHS1, and 3 with neurologic phenotype. There was an increased risk of prenatal or neonatal death within this group (6 deaths were in utero or within 2 months of life; 6 pregnancies were terminated). Incidence of polyhydramnios, congenital anomalies (eg, diaphragmatic hernia), and dysmorphism was significantly increased. Biallelic missense or mixed genotype were reported in the remaining 45 cases-32 showed a neurologic phenotype and 12 had MCAHS1. No cases of diaphragmatic hernia or abdominal wall defects were seen in this group except patient 1 in which we found the missense variant p.Ser893Arg to result in functionally null alleles, suggesting the possibility of an undescribed functionally important region in the final exon.; Changed publications: 36322149; Changed phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563, Fryns syndrome
Mendeliome v1.486 SEC16B Zornitza Stark Gene: sec16b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.486 SEC16B Zornitza Stark Classified gene: SEC16B as Amber List (moderate evidence)
Mendeliome v1.486 SEC16B Zornitza Stark Gene: sec16b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.484 ADAMTS9 Zornitza Stark Phenotypes for gene: ADAMTS9 were changed from Nephronophthisis-Related Ciliopathy to Nephropathy-related ciliopathy, MONDO:0022409, ADAMTS9-related
Mendeliome v1.483 NDUFB7 Zornitza Stark Phenotypes for gene: NDUFB7 were changed from Congenital lactic acidosis; hypertrophic cardiomyopathy to Mitochondrial complex I deficiency nuclear type 39 (MC1DN39), MIM#620135; Congenital lactic acidosis; hypertrophic cardiomyopathy
Mendeliome v1.482 ADAMTS9 Chirag Patel Classified gene: ADAMTS9 as Amber List (moderate evidence)
Mendeliome v1.482 ADAMTS9 Chirag Patel Gene: adamts9 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.480 AFDN Zornitza Stark Gene: afdn has been classified as Red List (Low Evidence).
Mendeliome v1.480 AFDN Zornitza Stark gene: AFDN was added
gene: AFDN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AFDN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AFDN were set to 36384317
Phenotypes for gene: AFDN were set to Cleft lip/palate, MONDO:0016044, AFDN-related
Review for gene: AFDN was set to RED
Added comment: Over-representation of rare AFDN missense variants reported in a cohort of CL/P individuals of African and Brazilian origin. However, almost all of the variants reported have hets in gnomad. The one that is novel has alternative missense at the same aa position.
Sources: Literature
Mendeliome v1.478 FOXI1 Zornitza Stark reviewed gene: FOXI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal recessive distal renal tubular acidosis MONDO:0018440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.478 CLEC3B Zornitza Stark Gene: clec3b has been classified as Green List (High Evidence).
Mendeliome v1.478 CLEC3B Zornitza Stark Classified gene: CLEC3B as Green List (high evidence)
Mendeliome v1.478 CLEC3B Zornitza Stark Gene: clec3b has been classified as Green List (High Evidence).
Mendeliome v1.477 CLEC3B Chirag Patel gene: CLEC3B was added
gene: CLEC3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLEC3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLEC3B were set to PMID: 35331648
Phenotypes for gene: CLEC3B were set to Macular dystrophy, retinal, 4, OMIM #619977
Review for gene: CLEC3B was set to GREEN
Added comment: 12 affected individuals from 5 multigenerational Japanese families in a small village in Miyazaki diagnosed with autosomal dominant maculoretinopathy. WES identified a pathogenic variant (p.Ala180Asp) in CLEC3B, which encodes tetranectin, a plasminogen kringle-4 binding protein. Variant cosegregated with the ocular phenotype.

Mice that received subretinal injections with CLEC3B variant displayed multiple subretinal hyperreflective deposits, reduced retinal thickness, and decreased electroretinographic responses. The optokinetic tracking response indicated that spatial frequency was significantly lower (P < .05), implying impaired visual function in the mice.
Sources: Literature
Mendeliome v1.476 ARPC4 Zornitza Stark Phenotypes for gene: ARPC4 were changed from Microcephaly; mild motor delays; significant speech impairment to Neurodevelopmental disorder, ARPC4-related MONDO#0700092
Mendeliome v1.475 SPTBN5 Zornitza Stark Classified gene: SPTBN5 as Red List (low evidence)
Mendeliome v1.475 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Red List (Low Evidence).
Mendeliome v1.474 SPTBN5 Zornitza Stark edited their review of gene: SPTBN5: Added comment: Some of the missense variants are present at high population frequencies, not compatible with Mendelian disease. Gene is tolerant of LoF in gnomad, raising questions about the pathogenicity of the LoF variant.
Commentaries questioning gene-disease relationship PMID: 36117916; 36238261; Changed rating: RED
Mendeliome v1.473 MTSS1 Zornitza Stark Gene: mtss1 has been classified as Green List (High Evidence).
Mendeliome v1.473 MTSS1 Zornitza Stark Classified gene: MTSS1 as Green List (high evidence)
Mendeliome v1.473 MTSS1 Zornitza Stark Gene: mtss1 has been classified as Green List (High Evidence).
Mendeliome v1.472 MTSS1 Zornitza Stark gene: MTSS1 was added
gene: MTSS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MTSS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTSS1 were set to 36067766
Phenotypes for gene: MTSS1 were set to Intellectual disability, MTSS1-related (MONDO#0001071)
Review for gene: MTSS1 was set to GREEN
Added comment: Five individuals with the same heterozygous de novo variant in MTSS2 (NM_138383.2: c.2011C>T [p.Arg671Trp]) identified by exome sequencing.

The individuals presented with global developmental delay, mild intellectual disability, ophthalmological anomalies, microcephaly or relative microcephaly, and shared mild facial dysmorphisms.

Immunoblots of fibroblasts from two affected individuals revealed that the variant does not significantly alter MTSS2 levels. We modeled the variant in Drosophila and showed that the fly ortholog missing-in-metastasis (mim) was widely expressed in most neurons and a subset of glia of the CNS. Loss of mim led to a reduction in lifespan, impaired locomotor behavior, and reduced synaptic transmission in adult flies. Expression of the human MTSS2 reference cDNA rescued the mim loss-of-function (LoF) phenotypes, whereas the c.2011C>T variant had decreased rescue ability compared to the reference, suggesting it is a partial LoF allele. However, elevated expression of the variant, but not the reference MTSS2 cDNA, led to similar defects as observed by mim LoF, suggesting that the variant is toxic and may act as a dominant-negative allele when expressed in flies.
Sources: Literature
Mendeliome v1.470 TPR Zornitza Stark Gene: tpr has been classified as Red List (Low Evidence).
Mendeliome v1.470 TPR Zornitza Stark Classified gene: TPR as Red List (low evidence)
Mendeliome v1.470 TPR Zornitza Stark Gene: tpr has been classified as Red List (Low Evidence).
Mendeliome v1.469 SMC5 Zornitza Stark Gene: smc5 has been classified as Green List (High Evidence).
Mendeliome v1.469 SMC5 Zornitza Stark Classified gene: SMC5 as Green List (high evidence)
Mendeliome v1.469 SMC5 Zornitza Stark Gene: smc5 has been classified as Green List (High Evidence).
Mendeliome v1.467 SLF2 Zornitza Stark Gene: slf2 has been classified as Green List (High Evidence).
Mendeliome v1.467 SLF2 Zornitza Stark Classified gene: SLF2 as Green List (high evidence)
Mendeliome v1.467 SLF2 Zornitza Stark Gene: slf2 has been classified as Green List (High Evidence).
Mendeliome v1.465 TPR Achchuthan Shanmugasundram gene: TPR was added
gene: TPR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPR were set to 34494102
Phenotypes for gene: TPR were set to intellectual disability, MONDO:0001071; cerebellar ataxia, MONDO:0000437; microcephaly, MONDO:0001149
Review for gene: TPR was set to RED
Added comment: This gene should be added to the following diseases: Intellectual disability, microcephaly and ataxia.

Comment on classification of this gene: This gene should be added with a RED rating as the association is based on biallelic variants identified from a report of two siblings.

Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability.

Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Mendeliome v1.465 NF1 Achchuthan Shanmugasundram reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34476477; Phenotypes: Neurofibromatosis, type 1, MIM# 162200, MONDO:0018975, renovascular hypertension, MONDO:0006947; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.464 IRF2BP2 Zornitza Stark Classified gene: IRF2BP2 as Green List (high evidence)
Mendeliome v1.464 IRF2BP2 Zornitza Stark Gene: irf2bp2 has been classified as Green List (High Evidence).
Mendeliome v1.463 IRF2BP2 Zornitza Stark edited their review of gene: IRF2BP2: Added comment: Reports of additional patients: 4yo with chronic diarrhea, severe eczema, anemia, failure to thrive, fevers, short stature, recurrent infections, cataracts, hypodontia, hypotrichosis alopecia, hypogammaglobulinemia. The 33-year-old male presented with recurrent respiratory infections since childhood, colitis and RA beginning at age 25 years.; Changed rating: GREEN; Changed publications: 27016798, 32048120, 36193988, 33864888; Changed phenotypes: Immunodeficiency, common variable, 14, MIM# 617765
Mendeliome v1.462 ATP5F1 Zornitza Stark Gene: atp5f1 has been classified as Red List (Low Evidence).
Mendeliome v1.461 DUOX2 Zornitza Stark Classified gene: DUOX2 as Green List (high evidence)
Mendeliome v1.461 DUOX2 Zornitza Stark Gene: duox2 has been classified as Green List (High Evidence).
Mendeliome v1.459 RPS6KB1 Arina Puzriakova gene: RPS6KB1 was added
gene: RPS6KB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPS6KB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPS6KB1 were set to 34916228
Phenotypes for gene: RPS6KB1 were set to Hypertrophic cardiomyopathy
Review for gene: RPS6KB1 was set to GREEN
Added comment: Jain et al. 2022 (PMID: 34916228) reported on two unrelated HCM families with the same heterozygous missense RPS6KB1 variant (p.G47W), and subsequently three further unrelated probands with HCM harbouring distinct heterozygous variants (p.Q49K, p.Y62H, respectively). Variants segregated with disease, were predicted pathogenic by silico analyses and were ultrarare or absent in population databases. Functional studies in the HL-1 (mouse cardiomyocytes) cells showed that the patient-specific RPS6KB1 mutant significantly increased cell size and activated rpS6 and ERK1/2 signalling cascades. The relationship between RPS6KB1 and cardiac hypertrophy has also been explored in feline and mice models (PMID: 15226426; 17976640)
Sources: Literature
Mendeliome v1.456 ITPR3 Zornitza Stark Classified gene: ITPR3 as Green List (high evidence)
Mendeliome v1.456 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Green List (High Evidence).
Mendeliome v1.453 WDR5 Bryony Thompson Gene: wdr5 has been classified as Green List (High Evidence).
Mendeliome v1.453 WDR5 Bryony Thompson Classified gene: WDR5 as Green List (high evidence)
Mendeliome v1.453 WDR5 Bryony Thompson Gene: wdr5 has been classified as Green List (High Evidence).
Mendeliome v1.452 WDR5 Bryony Thompson gene: WDR5 was added
gene: WDR5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR5 were set to DOI:https://doi.org/10.1016/j.xhgg.2022.100157
Phenotypes for gene: WDR5 were set to Neurodevelopmental disorder MONDO:0700092, WDR5-related
Mode of pathogenicity for gene: WDR5 was set to Other
Review for gene: WDR5 was set to GREEN
Added comment: Six different missense variants were identified (de novo) in 11 affected individuals with neurodevelopmental disorders, with a broad spectrum of additional features, including epilepsy, aberrant growth parameters, skeletal and cardiac abnormalities. In vivo and in vitro functional suggest that loss-of-function is not the mechanism of disease. The mechanism of disease is yet to be established.
Sources: Literature
Mendeliome v1.447 DNAJB4 Zornitza Stark Gene: dnajb4 has been classified as Green List (High Evidence).
Mendeliome v1.447 DNAJB4 Zornitza Stark Classified gene: DNAJB4 as Green List (high evidence)
Mendeliome v1.447 DNAJB4 Zornitza Stark Gene: dnajb4 has been classified as Green List (High Evidence).
Mendeliome v1.445 PI4K2A Seb Lunke Classified gene: PI4K2A as Green List (high evidence)
Mendeliome v1.445 PI4K2A Seb Lunke Gene: pi4k2a has been classified as Green List (High Evidence).
Mendeliome v1.444 MYCBP2 Zornitza Stark Gene: mycbp2 has been classified as Green List (High Evidence).
Mendeliome v1.444 MYCBP2 Zornitza Stark Classified gene: MYCBP2 as Green List (high evidence)
Mendeliome v1.444 MYCBP2 Zornitza Stark Gene: mycbp2 has been classified as Green List (High Evidence).
Mendeliome v1.443 CAMSAP1 Zornitza Stark Gene: camsap1 has been classified as Green List (High Evidence).
Mendeliome v1.443 CAMSAP1 Zornitza Stark Classified gene: CAMSAP1 as Green List (high evidence)
Mendeliome v1.443 CAMSAP1 Zornitza Stark Gene: camsap1 has been classified as Green List (High Evidence).
Mendeliome v1.442 THAP1 Michelle Torres commented on gene: THAP1: Monoallelic is well established with reduced penetrance.

Biallelic was seen in 3 families generally with severe and early onset dystonia:

PMID: 36205328: consanguineous family (gene panel), proband homozygous for p.Lys162Asn with early onset multifocal dystonia with severe oromandibular/laryngeal dysfunction; both parents were confirmed carriers with milder features (47 yo father with tightness and difficulty with fine motor tasks, 41 yo mother with tightness).

PMID: 21425335: 3 siblings are homozygous for the p.Leu32His with early-onset generalized dystonia. Carriers were unaffected.

PMID: 20211909: a homozygous variant was identified in an individual with with writer's dystonia initially and then developing segmental dystonia, onset at 57 yo, parents could not be tested.
Mendeliome v1.442 CAMSAP1 Naomi Baker gene: CAMSAP1 was added
gene: CAMSAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to lissencephaly spectrum disorders (MONDO:0018838), CAMSAP1-related
Review for gene: CAMSAP1 was set to GREEN
Added comment: Five unrelated families with bi-allelic loss-of-function variants. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe neurodevelopmental delay, cortical visual impairment, and seizures.
Sources: Literature
Mendeliome v1.442 THAP1 Michelle Torres reviewed gene: THAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36205328, 21425335, 20211909; Phenotypes: Dystonia 6, torsion, (MIM#60262); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.442 KLHL20 Zornitza Stark Gene: klhl20 has been classified as Green List (High Evidence).
Mendeliome v1.442 KLHL20 Zornitza Stark Classified gene: KLHL20 as Green List (high evidence)
Mendeliome v1.442 KLHL20 Zornitza Stark Gene: klhl20 has been classified as Green List (High Evidence).
Mendeliome v1.441 FICD Alison Yeung Gene: ficd has been classified as Green List (High Evidence).
Mendeliome v1.441 FICD Alison Yeung Classified gene: FICD as Green List (high evidence)
Mendeliome v1.441 FICD Alison Yeung Gene: ficd has been classified as Green List (High Evidence).
Mendeliome v1.440 FICD Alison Yeung gene: FICD was added
gene: FICD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FICD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FICD were set to 36136088
Phenotypes for gene: FICD were set to Hereditary motor neurone disease, FICD-related, MONDO:0024257
Review for gene: FICD was set to GREEN
Added comment: Three unrelated families with recurrent homozygous missense variant: p.Arg374His
One further family with Chet variants: p.Arg 374His and p.Gly370GlufsTer53

Fibroblasts from patients with FICD variants have abnormally increased levels of AMPylated and thus inactivated BiP.

Onset of symptoms in childhood with progressive course. Presentation with severe lower limb spasticity and mild upper limb spascticity, nerve conduction test shows motor neuropathy.
Sources: Literature
Mendeliome v1.439 FOXI3 Zornitza Stark Gene: foxi3 has been classified as Green List (High Evidence).
Mendeliome v1.438 FOXI3 Zornitza Stark Classified gene: FOXI3 as Green List (high evidence)
Mendeliome v1.438 FOXI3 Zornitza Stark Gene: foxi3 has been classified as Green List (High Evidence).
Mendeliome v1.437 FOXI3 Paul De Fazio gene: FOXI3 was added
gene: FOXI3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXI3 were set to 36260083
Phenotypes for gene: FOXI3 were set to Dysostosis with predominant craniofacial involvement (MONDO:0800085)
Penetrance for gene: FOXI3 were set to Incomplete
Review for gene: FOXI3 was set to GREEN
gene: FOXI3 was marked as current diagnostic
Added comment: Ten affected individuals from 4 families reported with monoallelic variants, 2 with missense variants affecting the nuclear localisation sequence and 2 with frameshift variants.

The missense variants were associated with isolated microtia with aural atresia and affected subcellular localisation of the protein, while the frameshift variants were associated with microtia and mandubular hypoplasia, suggesting dosage sensitivity.

Rated green but CAUTION for incomplete penetrance. 3 of the 4 families had unaffected carriers. Family 1 in particular had 25 genotyped individuals, of which 15 were carriers, of which 5 were affected.
Sources: Literature
Mendeliome v1.436 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Added comment: Second family reported in PMID 36282599: single affected individual with homozygous missense variant; clinical presentation with progeroid features but functional data supports underlying mitochondrial aetiology.

Maintain Amber rating as the two patients have quite disparate clinical presentations.; Changed publications: 36282599
Mendeliome v1.436 CBFB Ain Roesley Gene: cbfb has been classified as Green List (High Evidence).
Mendeliome v1.436 CBFB Ain Roesley Classified gene: CBFB as Green List (high evidence)
Mendeliome v1.436 CBFB Ain Roesley Gene: cbfb has been classified as Green List (High Evidence).
Mendeliome v1.435 CBFB Ain Roesley gene: CBFB was added
gene: CBFB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CBFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBFB were set to 36241386
Phenotypes for gene: CBFB were set to cleidocranial dysplasia (MONDO#0007340), CBFB-related
Penetrance for gene: CBFB were set to Complete
Review for gene: CBFB was set to GREEN
gene: CBFB was marked as current diagnostic
Added comment: 5 families with 8 individuals, including 2 de novos and 1 intragenic exon 4 deletion

In 1 family, the mother did not report skeletal concerns but had dental abnormalities during childhood
Sources: Literature
Mendeliome v1.432 CEBPE Zornitza Stark edited their review of gene: CEBPE: Added comment: Additional family with auto inflammatory phenotype published in 31201888, extensive functional data.; Changed publications: 10359588, 11313242, 31256937, 29651288, 31201888
Mendeliome v1.431 SFTPA1 Zornitza Stark Classified gene: SFTPA1 as Green List (high evidence)
Mendeliome v1.431 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Green List (High Evidence).
Mendeliome v1.430 GNPNAT1 Krithika Murali reviewed gene: GNPNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36097642, 35427807; Phenotypes: Rhizomelic dysplasia, Ain-Naz type, MIM#619598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.428 FGL2 Zornitza Stark Gene: fgl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.428 FGL2 Zornitza Stark Classified gene: FGL2 as Amber List (moderate evidence)
Mendeliome v1.428 FGL2 Zornitza Stark Gene: fgl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.426 SP6 Zornitza Stark Phenotypes for gene: SP6 were changed from hypoplastic amelogenesis imperfecta to Amelogenesis imperfecta, type IK, MIM# 620104
Mendeliome v1.425 SP6 Zornitza Stark edited their review of gene: SP6: Changed phenotypes: Amelogenesis imperfecta, type IK, MIM# 620104
Mendeliome v1.422 PAX4 Zornitza Stark Classified gene: PAX4 as Red List (low evidence)
Mendeliome v1.422 PAX4 Zornitza Stark Gene: pax4 has been classified as Red List (Low Evidence).
Mendeliome v1.421 CLCN7 Zornitza Stark changed review comment from: Two individuals reported with same missense variant and hypopigmentation, organomegaly, and delayed myelination and development. Variant is GoF. No osteopetrosis, biopsy findings from skin and other organs are consistent with a lysosomal storage disorder. IUGR, prematurity and polyhydramnios are features.

Bi-allelic variants in this gene are associated with osteopetrosis.; to: Two individuals reported with same missense variant and hypopigmentation, organomegaly, and delayed myelination and development. Variant is GoF. No osteopetrosis, biopsy findings from skin and other organs are consistent with a lysosomal storage disorder. IUGR, prematurity and polyhydramnios are features.

Mono- and bi-allelic variants in this gene are associated with osteopetrosis.
Mendeliome v1.421 CLCN7 Zornitza Stark edited their review of gene: CLCN7: Changed phenotypes: Hypopigmentation, organomegaly, and delayed myelination and development, MIM# 618541, Osteopetrosis, autosomal dominant 2, MIM# 166600, Osteopetrosis, autosomal recessive 4, MIM# 611490
Mendeliome v1.419 PRDM16 Zornitza Stark Classified gene: PRDM16 as Green List (high evidence)
Mendeliome v1.419 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Green List (High Evidence).
Mendeliome v1.416 CCDC34 Zornitza Stark Gene: ccdc34 has been classified as Green List (High Evidence).
Mendeliome v1.416 CCDC34 Zornitza Stark Classified gene: CCDC34 as Green List (high evidence)
Mendeliome v1.416 CCDC34 Zornitza Stark Gene: ccdc34 has been classified as Green List (High Evidence).
Mendeliome v1.414 ACTN2 Bryony Thompson reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17097056, 20022194, 25173926, 25224718, 22767232, 27287556, 28436997, 31333075, 31956495, 32973354, 34802252, 33500567, 36078153, 36116040; Phenotypes: intrinsic cardiomyopathy MONDO:0000591; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.412 NFAT5 Zornitza Stark Classified gene: NFAT5 as Amber List (moderate evidence)
Mendeliome v1.412 NFAT5 Zornitza Stark Gene: nfat5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.410 LAMA5 Zornitza Stark Phenotypes for gene: LAMA5 were changed from bent bone dysplasia; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay to Bent bone dysplasia syndrome 2, MIM# 620076; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay
Mendeliome v1.409 LAMA5 Zornitza Stark edited their review of gene: LAMA5: Changed phenotypes: Nephrotic syndrome, type 26 620049, Bent bone dysplasia syndrome 2, MIM# 620076
Mendeliome v1.408 FGF14 Zornitza Stark Phenotypes for gene: FGF14 were changed from Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003 to Spinocerebellar ataxia 27, MIM# 609307; Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003
Mendeliome v1.407 FGF14 Zornitza Stark edited their review of gene: FGF14: Changed phenotypes: Spinocerebellar ataxia 27, MIM# 609307, Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003
Mendeliome v1.407 FGF14 Zornitza Stark Phenotypes for gene: FGF14 were changed from Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227 to Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003
Mendeliome v1.406 FGF14 Zornitza Stark reviewed gene: FGF14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.406 IMPA1 Bryony Thompson Gene: impa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.406 IMPA1 Bryony Thompson Classified gene: IMPA1 as Amber List (moderate evidence)
Mendeliome v1.406 IMPA1 Bryony Thompson Gene: impa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.405 IMPA1 Bryony Thompson gene: IMPA1 was added
gene: IMPA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IMPA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IMPA1 were set to 26416544; 24554717; 32839513; 17460611
Phenotypes for gene: IMPA1 were set to intellectual disability, autosomal recessive 59 MONDO:0015020
Review for gene: IMPA1 was set to AMBER
Added comment: A homozygous frameshift variant identified in a large Brazilian consanguineous family with ID, also supporting functional studies and null mouse models.
Sources: Literature
Mendeliome v1.404 ARNT2 Bryony Thompson Gene: arnt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.404 ARNT2 Bryony Thompson Classified gene: ARNT2 as Amber List (moderate evidence)
Mendeliome v1.404 ARNT2 Bryony Thompson Gene: arnt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.403 ARNT2 Bryony Thompson gene: ARNT2 was added
gene: ARNT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARNT2 were set to 11381139; 24022475
Phenotypes for gene: ARNT2 were set to Webb-Dattani syndrome MONDO:0014404
Review for gene: ARNT2 was set to AMBER
Added comment: A homozygous frameshift (c.1373_1374dupTC) in six affected children from a highly consanguineous family with a syndromic phenotype including microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract. In a Arnt2(-/-) mouse model embryos die perinatally and exhibit impaired hypothalamic development.
Sources: Literature
Mendeliome v1.402 FRMD5 Zornitza Stark Gene: frmd5 has been classified as Green List (High Evidence).
Mendeliome v1.402 FRMD5 Zornitza Stark Classified gene: FRMD5 as Green List (high evidence)
Mendeliome v1.402 FRMD5 Zornitza Stark Gene: frmd5 has been classified as Green List (High Evidence).
Mendeliome v1.398 GIGYF1 Elena Savva Classified gene: GIGYF1 as Green List (high evidence)
Mendeliome v1.398 GIGYF1 Elena Savva Gene: gigyf1 has been classified as Green List (High Evidence).
Mendeliome v1.396 TOMM7 Bryony Thompson Gene: tomm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.396 TOMM7 Bryony Thompson Classified gene: TOMM7 as Amber List (moderate evidence)
Mendeliome v1.396 TOMM7 Bryony Thompson Gene: tomm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.395 TOMM7 Bryony Thompson gene: TOMM7 was added
gene: TOMM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to DOI:https://doi.org/10.1016/j.xhgg.2022.100148
Phenotypes for gene: TOMM7 were set to growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy MONDO:0014911
Review for gene: TOMM7 was set to AMBER
Added comment: A single case identified with a homozygous variant in TOMM7 (c.73T>C, p.Trp25Arg) that presented with syndromic short stature, skeletal abnormalities, muscle hypotonia, microvesicular liver steatosis, and developmental delay. A mouse model of the missense variant demonstrated a bioenergetic defect and a phenotype of mitochondrial diseases. It also strongly suggested that the variant is hypomorphic because mice homozygous for this variant showed a milder phenotype than those with a homozygous Tomm7 deletion.
Sources: Literature
Mendeliome v1.393 SEPT4 Bryony Thompson Gene: sept4 has been classified as Green List (High Evidence).
Mendeliome v1.393 SEPT4 Bryony Thompson Classified gene: SEPT4 as Green List (high evidence)
Mendeliome v1.393 SEPT4 Bryony Thompson Gene: sept4 has been classified as Green List (High Evidence).
Mendeliome v1.391 FAM20B Bryony Thompson Gene: fam20b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.391 FAM20B Bryony Thompson Classified gene: FAM20B as Amber List (moderate evidence)
Mendeliome v1.391 FAM20B Bryony Thompson Gene: fam20b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.390 FAM20B Bryony Thompson gene: FAM20B was added
gene: FAM20B was added to Mendeliome. Sources: Other
Mode of inheritance for gene: FAM20B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20B were set to 30847897; 30105814; 22732358; 27405802
Phenotypes for gene: FAM20B were set to Desbuquois dysplasia MONDO:0015426
Review for gene: FAM20B was set to AMBER
Added comment: Two siblings from a single family with neonatal short limb dysplasia resembling Desbuquois dysplasia. One of the siblings underwent genetic testing and compound heterozygous variants were identified in FAM20B ((NM_014864: c.174_178delTACCT p.T59Afs*19/c.1038delG p.N347Mfs*4). Multiple mouse models reported with skeletal abnormalities.
Sources: Other
Mendeliome v1.389 EXOC6B Bryony Thompson Gene: exoc6b has been classified as Green List (High Evidence).
Mendeliome v1.389 EXOC6B Bryony Thompson Classified gene: EXOC6B as Green List (high evidence)
Mendeliome v1.389 EXOC6B Bryony Thompson Gene: exoc6b has been classified as Green List (High Evidence).
Mendeliome v1.388 EXOC6B Bryony Thompson gene: EXOC6B was added
gene: EXOC6B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC6B were set to 26669664; 30284759; 36150098
Phenotypes for gene: EXOC6B were set to Spondyloepimetaphyseal dysplasia with joint laxity MONDO:0019675
Review for gene: EXOC6B was set to GREEN
Added comment: 6 affected individuals from 4 families, and supporting assays in patient cells
PMID: 26669664 - 2 brothers with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones from a consanguineous family, with a homozygous nonsense variant [c.906T>A/p.(Tyr302*)]
PMID: 30284759 - 2 sisters with dislocations of the hips and knees, long slender fingers with distal tapering, significant motor disability but normal (older sister) or low-normal intelligence (younger sister), with a homozygous in-frame deletion of exons 9-20
PMID: 36150098 - 2 unrelated probands from consanguineous families, one with a homozygous frameshift exon 20 deletion and one with a homozygous nonsense variant (c.401T>G p.Leu134Ter). Function assessment of patient fibroblast cell lines indicated abrogation of exocytosis leading to impaired primary ciliogenesis
Sources: Literature
Mendeliome v1.386 VPS33A Bryony Thompson Classified gene: VPS33A as Green List (high evidence)
Mendeliome v1.386 VPS33A Bryony Thompson Gene: vps33a has been classified as Green List (High Evidence).
Mendeliome v1.385 VPS33A Bryony Thompson changed review comment from: PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells.
PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family
PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family
PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts; to: Now two missense variants reported with disease in at least 15 probands/families
PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells.
PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family
PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family
PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts
Mendeliome v1.385 DPH5 Zornitza Stark Gene: dph5 has been classified as Green List (High Evidence).
Mendeliome v1.385 DPH5 Zornitza Stark Classified gene: DPH5 as Green List (high evidence)
Mendeliome v1.385 DPH5 Zornitza Stark Gene: dph5 has been classified as Green List (High Evidence).
Mendeliome v1.384 DPH5 Zornitza Stark gene: DPH5 was added
gene: DPH5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DPH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPH5 were set to 35482014
Phenotypes for gene: DPH5 were set to Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, MIM# 620070
Review for gene: DPH5 was set to GREEN
Added comment: 5 individuals from 3 unrelated families reported with severe ID, feeding difficulties, dysmorphic features and congenital anomalies, though there was no consistent pattern to these.
Sources: Literature
Mendeliome v1.383 VPS33A Bryony Thompson reviewed gene: VPS33A: Rating: GREEN; Mode of pathogenicity: None; Publications: 28013294, 27547915, 31936524, 36153662; Phenotypes: Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders MONDO:0015012; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.383 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Intermediate CMT to Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Charcot-Marie-Tooth disease, axonal, type 2II , MIM#620068
Mendeliome v1.382 SLC12A6 Zornitza Stark edited their review of gene: SLC12A6: Changed phenotypes: Andermann syndrome, Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800, Charcot-Marie-Tooth disease, axonal, type 2II , MIM#620068
Mendeliome v1.376 SCNM1 Elena Savva Gene: scnm1 has been classified as Green List (High Evidence).
Mendeliome v1.376 SCNM1 Elena Savva Classified gene: SCNM1 as Green List (high evidence)
Mendeliome v1.376 SCNM1 Elena Savva Gene: scnm1 has been classified as Green List (High Evidence).
Mendeliome v1.374 LETM1 Zornitza Stark Gene: letm1 has been classified as Green List (High Evidence).
Mendeliome v1.374 LETM1 Zornitza Stark Classified gene: LETM1 as Green List (high evidence)
Mendeliome v1.374 LETM1 Zornitza Stark Gene: letm1 has been classified as Green List (High Evidence).
Mendeliome v1.373 DACT1 Zornitza Stark Classified gene: DACT1 as Amber List (moderate evidence)
Mendeliome v1.373 DACT1 Zornitza Stark Gene: dact1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.372 GABRG1 Seb Lunke Gene: gabrg1 has been classified as Red List (Low Evidence).
Mendeliome v1.372 GABBR1 Zornitza Stark Gene: gabbr1 has been classified as Green List (High Evidence).
Mendeliome v1.372 GABBR1 Zornitza Stark Classified gene: GABBR1 as Green List (high evidence)
Mendeliome v1.372 GABBR1 Zornitza Stark Gene: gabbr1 has been classified as Green List (High Evidence).
Mendeliome v1.371 GABRG1 Seb Lunke Classified gene: GABRG1 as Red List (low evidence)
Mendeliome v1.371 GABRG1 Seb Lunke Gene: gabrg1 has been classified as Red List (Low Evidence).
Mendeliome v1.370 DUT Seb Lunke Gene: dut has been classified as Green List (High Evidence).
Mendeliome v1.370 DUT Seb Lunke Classified gene: DUT as Green List (high evidence)
Mendeliome v1.370 DUT Seb Lunke Gene: dut has been classified as Green List (High Evidence).
Mendeliome v1.369 DUT Daniel Flanagan gene: DUT was added
gene: DUT was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DUT were set to 28073829; 35611808
Phenotypes for gene: DUT were set to Bone marrow failure and diabetes mellitus syndrome (MIM#620044)
Review for gene: DUT was set to GREEN
Added comment: Homozygous missense (p.(Tyr142Cys)) identified in eight affected individuals from four unrelated consanguineous families (French, Egyptian, two Libyan) with diabetes and bone marrow failure. DUT silencing in human and rat pancreatic b-cells results in apoptosis via the intrinsic cell death pathway.

p.(Tyr142Cys) has 11 heterozygotes and no homozygotes in gnomAD.
Sources: Expert list
Mendeliome v1.369 CENPP Seb Lunke Gene: cenpp has been classified as Red List (Low Evidence).
Mendeliome v1.369 CENPP Seb Lunke changed review comment from: Sources: Literature; to: Single family with dominant SNHL segregated through 5 family members. Truncating variant in NM_001012267.3(CENPP):c.849T>A (p.Cys283Ter). Note: misannotated as nonsense variant in paper.
Sources: Literature
Mendeliome v1.368 SLC13A1 Zornitza Stark Gene: slc13a1 has been classified as Red List (Low Evidence).
Mendeliome v1.368 SLC13A1 Zornitza Stark Classified gene: SLC13A1 as Red List (low evidence)
Mendeliome v1.368 SLC13A1 Zornitza Stark Gene: slc13a1 has been classified as Red List (Low Evidence).
Mendeliome v1.367 MED11 Ain Roesley Gene: med11 has been classified as Green List (High Evidence).
Mendeliome v1.367 MED11 Ain Roesley Classified gene: MED11 as Green List (high evidence)
Mendeliome v1.367 MED11 Ain Roesley Gene: med11 has been classified as Green List (High Evidence).
Mendeliome v1.366 MED11 Ain Roesley gene: MED11 was added
gene: MED11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to neurodevelopmental disorder MONDO#0700092, MED11-related
Review for gene: MED11 was set to GREEN
gene: MED11 was marked as current diagnostic
Added comment: 7 affected from 5 families (3x consang) with the same recurrent variant of p.(Arg109*).

Protein truncating, NOT NMD as proven by RT-PCR and western blot. Zebrafish knockout model recapitulates key clinical phenotypes

NO evidence of founder effect from haplotype analysis

7/7 cerebral dysgyria, cortical atrophy
5/7 limb contracture
4/7 epilepsy
3/7 families with IUGR
3/7 GDD
3/7 hearing loss
3/7 undescended testis
2/7 nystagmus
1/7 congenital cataract
Sources: Literature
Mendeliome v1.365 ATP6V0C Alison Yeung Classified gene: ATP6V0C as Green List (high evidence)
Mendeliome v1.365 ATP6V0C Alison Yeung Gene: atp6v0c has been classified as Green List (High Evidence).
Mendeliome v1.364 LAMA5 Zornitza Stark Classified gene: LAMA5 as Green List (high evidence)
Mendeliome v1.364 LAMA5 Zornitza Stark Gene: lama5 has been classified as Green List (High Evidence).
Mendeliome v1.363 NAPB Alison Yeung Gene: napb has been classified as Green List (High Evidence).
Mendeliome v1.363 NAPB Alison Yeung Classified gene: NAPB as Green List (high evidence)
Mendeliome v1.363 NAPB Alison Yeung Gene: napb has been classified as Green List (High Evidence).
Mendeliome v1.362 FKBP6 Zornitza Stark Gene: fkbp6 has been classified as Green List (High Evidence).
Mendeliome v1.362 FKBP6 Zornitza Stark Classified gene: FKBP6 as Green List (high evidence)
Mendeliome v1.362 FKBP6 Zornitza Stark Gene: fkbp6 has been classified as Green List (High Evidence).
Mendeliome v1.361 MTSS1L Elena Savva Gene: mtss1l has been classified as Green List (High Evidence).
Mendeliome v1.361 SARS Ee Ming Wong edited their review of gene: SARS: Added comment: -Two missense variants within the aminoacylation domain identified in 16 affected individuals from 3 distinct CMT families
-Mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation; Changed rating: GREEN; Changed publications: 36088542; Changed phenotypes: Genetic peripheral neuropathy MONDO#0020127, SARS1-related
Mendeliome v1.361 FOSL2 Zornitza Stark Gene: fosl2 has been classified as Green List (High Evidence).
Mendeliome v1.361 FOSL2 Zornitza Stark Classified gene: FOSL2 as Green List (high evidence)
Mendeliome v1.361 FOSL2 Zornitza Stark Gene: fosl2 has been classified as Green List (High Evidence).
Mendeliome v1.360 MTSS1L Elena Savva Classified gene: MTSS1L as Green List (high evidence)
Mendeliome v1.360 MTSS1L Elena Savva Gene: mtss1l has been classified as Green List (High Evidence).
Mendeliome v1.359 MTSS1L Elena Savva gene: MTSS1L was added
gene: MTSS1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MTSS1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MTSS1L were set to PMID: 36067766
Phenotypes for gene: MTSS1L were set to Intellectual disability, MTSS2-related (MONDO#0001071)
Review for gene: MTSS1L was set to GREEN
Added comment: Alt gene name: MTSS2

Huang (2022): recurring de novo missense variant (p.R671W) causing syndromic intellectual disability in 5 unrelated individuals.
- Individuals present with GDD, mild ID (5/5), nystagmus (3/5), optic atrophy (1/5), ptosis (2/5), sensorineural hearing loss (2/4), microcephaly or relative microcephaly (5/5), and shared mild facial dysmorphisms.
- Overexpression supports a DN mechanism
Sources: Literature
Mendeliome v1.358 DAW1 Alison Yeung Gene: daw1 has been classified as Green List (High Evidence).
Mendeliome v1.358 DAW1 Alison Yeung Classified gene: DAW1 as Green List (high evidence)
Mendeliome v1.358 DAW1 Alison Yeung Gene: daw1 has been classified as Green List (High Evidence).
Mendeliome v1.357 DAW1 Alison Yeung gene: DAW1 was added
gene: DAW1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DAW1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAW1 were set to 36074124
Phenotypes for gene: DAW1 were set to Primary ciliary dyskinesia, MONDO:0016575; Visceral heterotaxy, MONDO:0018677
Review for gene: DAW1 was set to GREEN
Added comment: Biallelic variants identified in two unrelated families. Zebrafish model recapitulates PCD and heterotaxy phenotype
Sources: Literature
Mendeliome v1.356 RABGAP1 Zornitza Stark Gene: rabgap1 has been classified as Green List (High Evidence).
Mendeliome v1.356 RABGAP1 Zornitza Stark Classified gene: RABGAP1 as Green List (high evidence)
Mendeliome v1.356 RABGAP1 Zornitza Stark Gene: rabgap1 has been classified as Green List (High Evidence).
Mendeliome v1.354 NAPB Paul De Fazio gene: NAPB was added
gene: NAPB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAPB were set to 26235277; 28097321; 33189936
Phenotypes for gene: NAPB were set to Developmental and epileptic encephalopathy 107 MIM#620033
Review for gene: NAPB was set to GREEN
gene: NAPB was marked as current diagnostic
Added comment: PMID 26235277: homozygous nonsense variant identified in a 6 year old girl by trio WES with early-onset epileptic encephalopathy characterised by multifocal seizures and profound GDD

PMID 28097321: exome sequencing in 152 consanguineous families with at least one member affected with ID. Homozygous nonsense variant identified in a patient with profound ID, seizures, feeding difficulties in infancy, muscularhypotonia, microcephaly, and impaired vision

PMID 33189936: homozygous canonical splice variant identified by trio exome sequencing in two siblings with seizures, intellectual disability and global developmental delay, microcephaly (<-3SD), and muscular hypotonia.
Sources: Literature
Mendeliome v1.354 FKBP6 Dean Phelan gene: FKBP6 was added
gene: FKBP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FKBP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP6 were set to PMID: 36150389
Phenotypes for gene: FKBP6 were set to Spermatogenic failure (MONDO:0004983), FKBP6-related
Review for gene: FKBP6 was set to GREEN
Added comment: PMID: 36150389 - large cohort study of men with severe spermatogenic failure (SPGF), identified six individuals with rare bi-allelic loss of function variants in FKBP6. RT-qPCR and immunofluorescence confirmed lack of FKBP6 expression. In mice, Fkbp6 has also been shown to be essential for spermatogenesis.
Sources: Literature
Mendeliome v1.352 GCSH Ain Roesley Classified gene: GCSH as Green List (high evidence)
Mendeliome v1.352 GCSH Ain Roesley Gene: gcsh has been classified as Green List (High Evidence).
Mendeliome v1.348 FOSL2 Krithika Murali gene: FOSL2 was added
gene: FOSL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOSL2 were set to 36197437
Phenotypes for gene: FOSL2 were set to Neurodevelopmental disorder, MONDO:0700092, FOSL2-related
Review for gene: FOSL2 was set to GREEN
Added comment: PMID 36197437 Cospain et al 2022 report 11 individuals from 10 families with heterozygous PTC variants in exon 4/4 of the FOSL2 gene. All variants were predicted to escape NMD resulting in a truncated protein, with the truncation occurring proximal to the C-terminal domain (supportive functional studies).

In 10/11 families the variant occurred de novo in a single affected proband. In one family with 2 affected siblings, the variant was present in the siblings but absent in the unaffected parent likely due to gonadal mosaicism.

Clinical features included:
- Cutis aplasia congenital of the scalp (10/11)
- Tooth enamel hypoplasia and discolouration (8/9)
- Multiple other ectodermal features also noted e.g. small brittle nails, hypotrichosis/hypertrichosis, lichen sclerosis
- 5 individuals had cataracts (mostly bilateral, congenital/early childhood onset)
- 6/9 IUGR
- 5/9 postnatal growth restriction
- 7/9 developmental delay/ID
- 5/7 ADHD/ASD
- 2/9 seizures
Sources: Literature
Mendeliome v1.347 TRAF3 Zornitza Stark Classified gene: TRAF3 as Green List (high evidence)
Mendeliome v1.347 TRAF3 Zornitza Stark Gene: traf3 has been classified as Green List (High Evidence).
Mendeliome v1.346 TRAF3 Zornitza Stark changed review comment from: Single individual reported.; to: Single individual reported with HSV-induced encephalopathy.
Mendeliome v1.346 TRAF3 Zornitza Stark edited their review of gene: TRAF3: Added comment: PMID 35960817: Nine individuals from five unrelated families with childhood-onset immune diseases and recurrent infections. All patients had suffered recurrent ear and sinopulmonary infections, including pneumonias from encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenza, resulting in early-onset bronchiectasis in several individuals; Changed rating: GREEN; Changed publications: 20832341, 35960817; Changed phenotypes: Autoinflammatory syndrome, TRAF3-related, MONDO:0019751, hypergammaglobulinemia, lymphadenopathy, splenomegaly, Sjögren’s syndrome, {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5}, MIM# 614849
Mendeliome v1.346 KCNK3 Krithika Murali reviewed gene: KCNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36195757; Phenotypes: eurodevelopmental disorder, MONDO:0700092, KCNK3-related, developmental delay with sleep apnoea (DDSA), Pulmonary hypertension, primary, 4-MIM#615344; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.346 COQ4 Zornitza Stark changed review comment from: Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. At least 9 unrelated families reported.; to: Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. At least 9 unrelated families reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.
Mendeliome v1.346 ADAMTS19 Zornitza Stark Phenotypes for gene: ADAMTS19 were changed from Non-syndromic heart valve disease to Cardiac valvular dysplasia 2, MIM# 620067
Mendeliome v1.345 ADAMTS19 Zornitza Stark edited their review of gene: ADAMTS19: Changed phenotypes: Cardiac valvular dysplasia 2, MIM# 620067
Mendeliome v1.343 TYMS Zornitza Stark Phenotypes for gene: TYMS were changed from Dyskeratosis congenita MONDO:0015780 to Dyskeratosis congenita, digenic, MIM#620040
Mendeliome v1.342 TYMS Zornitza Stark edited their review of gene: TYMS: Changed phenotypes: Dyskeratosis congenita, digenic, MIM#620040
Mendeliome v1.342 ACVR1 Zornitza Stark changed review comment from: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.

Note variants in this gene are also associated with congenital heart disease, PMID 29089047.; to: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.

Clinical trial with palovarotene

Note variants in this gene are also associated with congenital heart disease, PMID 29089047.
Mendeliome v1.342 ATP7A Zornitza Stark changed review comment from: ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.; to: ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.

Treatment for Menkes disease: subcutaneous injections of copper histidine or copper chloride

ClinGen has assessed as moderate evidence for actionability.

Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms.
Mendeliome v1.341 PDCD6IP Zornitza Stark Phenotypes for gene: PDCD6IP were changed from Neurodevelopmental disorder MONDO:0700092; Microcephaly; intellectual disability to Microcephaly 29, primary, autosomal recessive, MIM# 620047; Microcephaly; intellectual disability
Mendeliome v1.340 PDCD6IP Zornitza Stark edited their review of gene: PDCD6IP: Changed phenotypes: Microcephaly 29, primary, autosomal recessive, MIM# 620047, Microcephaly, intellectual disability
Mendeliome v1.340 PDCD6IP Zornitza Stark edited their review of gene: PDCD6IP: Changed phenotypes: Microcephaly 29, primary, autosomal recessive , MIM# 620047, Microcephaly, intellectual disability
Mendeliome v1.340 DPP9 Zornitza Stark Gene: dpp9 has been classified as Green List (High Evidence).
Mendeliome v1.340 DPP9 Zornitza Stark Classified gene: DPP9 as Green List (high evidence)
Mendeliome v1.340 DPP9 Zornitza Stark Gene: dpp9 has been classified as Green List (High Evidence).
Mendeliome v1.338 AVPR2 Zornitza Stark reviewed gene: AVPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes insipidus, nephrogenic 304800, Nephrogenic syndrome of inappropriate antidiuresis 300539; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.338 AVP Zornitza Stark reviewed gene: AVP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes insipidus, neurohypophyseal MIM#125700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.338 AQP2 Zornitza Stark changed review comment from: Dominant disease is caused by variants exerting a dominant negative effect, whereas recessive disease is caused by bi-allelic loss of function variants.; to: Dominant disease is caused by variants exerting a dominant negative effect, whereas recessive disease is caused by bi-allelic loss of function variants.

Onset in infancy. Causes severe dehydration, can be life-threatening.

Treatment: hydration, low-salt, low-protein diet, thiazide diuretics, amiloride, indomethacin.

Clinical trials.
Mendeliome v1.338 APRT Zornitza Stark changed review comment from: APRT deficiency is an autosomal recessive metabolic disorder that can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA) in the kidney, which results in crystalluria and the formation of urinary stones. Clinical features include renal colic, hematuria, urinary tract infection, dysuria, and, in some cases, renal failure. The age at onset can range from 5 months to late adulthood; however, as many as 50% of APRT-deficient individuals may be asymptomatic.; to: APRT deficiency is an autosomal recessive metabolic disorder that can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA) in the kidney, which results in crystalluria and the formation of urinary stones. Clinical features include renal colic, hematuria, urinary tract infection, dysuria, and, in some cases, renal failure. The age at onset can range from 5 months to late adulthood; however, as many as 50% of APRT-deficient individuals may be asymptomatic.

Treatable: allopurinol or febuxostat, low purine diet.
Mendeliome v1.338 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features to Intestinal dysmotility syndrome, MIM# 620045; Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features
Mendeliome v1.334 NDNF Elena Savva Classified gene: NDNF as Amber List (moderate evidence)
Mendeliome v1.334 NDNF Elena Savva Gene: ndnf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.333 GIF Zornitza Stark Gene: gif has been classified as Green List (High Evidence).
Mendeliome v1.333 PTPA Zornitza Stark Gene: ptpa has been classified as Amber List (Moderate Evidence).
Mendeliome v1.333 PTPA Zornitza Stark Classified gene: PTPA as Amber List (moderate evidence)
Mendeliome v1.333 PTPA Zornitza Stark Gene: ptpa has been classified as Amber List (Moderate Evidence).
Mendeliome v1.332 PTPA Zornitza Stark gene: PTPA was added
gene: PTPA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPA were set to 36073231
Phenotypes for gene: PTPA were set to Intellectual disability, MONDO: 36073231, PTPA-related
Review for gene: PTPA was set to AMBER
Added comment: Biallelic PTPA pathogenic variants lead to a form of ID with later-onset parkinsonism based on 4 individuals from 2 families in the literature. Affected individuals were homozygous for missense variants demonstrated to result to reduced mRNA and protein levels as well as PP2A complex activation. Drosophila studies support an age-dependent locomotor dysfunction. Variants in other PP2A-complex-related genes also lead to NDDs. Summary provided below.

There is currently no associated phenotype in OMIM, G2P, PanelApp UK or SysID.

Consider inclusion in relevant panels (ID, Parkinsonism/movement disorders, etc) with amber rating pending further reports.

------

Fevga, Tesson et al (2022 - PMID: 36073231) describe the features of 4 individuals, from 2 unrelated families, with biallelic pathogenic PTPA variants.

These presented with normal or delayed early milestones, learning disability and ID (mild to moderate) followed by progressive signs of parkinsonism (at the age of 11 yrs in 2 sibs, 15 yrs in another individual). Motor symptoms were responsive to levodopa and later to deep brain stimulation.

Linkage analysis in one consanguineous family followed by exome revealed homozygosity for a missense PTPA variant (NM_178001:c.893T>G/p.Met298Arg). Exome sequencing in affected subjects from the 2nd family revealed homozygosity for a further missense variant (c.512C>A/p.Ala171Asp). There were no other candidate variants for the phenotype following parental / segregation studies.

Role of the gene:
As the authors discuss, PTPA (or PPP2R4) is ubiquitously expressed in all tissues incl. brain and encodes a phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase-2A (PP2A). PP2A in turn, is the major Ser/Thr phosphatase in brain targeting a large number of proteins involved in diverse functions. Activation of PP2A is dependent on its methylation, which is negatively regulated by the PP2A-specific methylesterase (PME-1). By binding to PME-1, PTPA counteracts the negative influence of the former on PP2A. Pathogenic variants in genes encoding subunits/regulators of the PP2A complex (e.g. PPP2R1A or PPP2CA) are associated with neurodevelopmental disorders.

Variant studies:
Upon overexpression of wt and both variants in a HEK-293 cell line the authors demonstrated that both variants resulted in significantly reduced mRNA and protein levels (which for Ala171Asp were attributed to increased proteasomal degradation). Both variants were shown to result in impaired PP2A complex activation compared to wt.

Drosophila / animal models:
Pan-neuronal RNAi-mediated knockdown of ptpa in Drosophila resulted in an age-dependent locomotor dysfunction, reversible with L-DOPA treatment.
Previous studies in mice suggest cognitive/electrophysiological impairments upon downregulation of PP2A activity in transgenic mice.
Sources: Literature
Mendeliome v1.331 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200 to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200; Nephrocalcinosis, MONDO:0001567, PKHD1-related
Mendeliome v1.328 PKHD1 Zornitza Stark edited their review of gene: PKHD1: Added comment: Notę heterozygous carriers reported to have liver cysts and nephrocalcinosis, gene-disease association considered MODERATE by ClinGen.; Changed publications: 28375157, 21945273; Changed phenotypes: Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200, Nephrocalcinosis, MONDO:0001567, PKHD1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.326 PPP2R5C Zornitza Stark Classified gene: PPP2R5C as Green List (high evidence)
Mendeliome v1.326 PPP2R5C Zornitza Stark Gene: ppp2r5c has been classified as Green List (High Evidence).
Mendeliome v1.324 NODAL Zornitza Stark Classified gene: NODAL as Amber List (moderate evidence)
Mendeliome v1.324 NODAL Zornitza Stark Gene: nodal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.323 NODAL Zornitza Stark edited their review of gene: NODAL: Added comment: NODAL is a good biological candidate for heterotaxy disorders, and this is supported by animal models. The gene is depleted for LoF variants in gnomad.

The missense variants reported in PMIDs 9354794 and 19064609 are present at a high population frequency in gnomad, including some in homozygous case: their association with disease is DISPUTED.

A total of at least 7 families reported with severe CHD and high impact variants (stop gain, frameshift and canonical splice site). However, almost invariably these were inherited from unaffected or questionably affected parents (e.g. self reports of heart murmur in childhood), raising questions about whether these variants contribute to disease under a monogenic or polygenic model and/or about penetrance.

Discussed at GenCC on 13/9/2022 and agreed on MODERATE assessment.; Changed rating: AMBER; Changed publications: 9354794, 19064609, 29368431, 19933292, 11311163, 30293987
Mendeliome v1.321 OOEP Bryony Thompson Classified gene: OOEP as Amber List (moderate evidence)
Mendeliome v1.321 OOEP Bryony Thompson Gene: ooep has been classified as Amber List (Moderate Evidence).
Mendeliome v1.320 UFSP2 Zornitza Stark Phenotypes for gene: UFSP2 were changed from Neurodevelopmental disorder; Hip dysplasia, Beukes type, MIM#142669; Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974 to Developmental and epileptic encephalopathy 106, MIM# 620028; Hip dysplasia, Beukes type, MIM#142669; Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974
Mendeliome v1.319 UFSP2 Zornitza Stark edited their review of gene: UFSP2: Changed phenotypes: Developmental and epileptic encephalopathy 106, MIM# 620028, Hip dysplasia, Beukes type, MIM#142669, Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974
Mendeliome v1.318 UBAP2L Zornitza Stark changed review comment from: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1).
Sources: Literature; to: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in 11 individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1).
Sources: Literature
Mendeliome v1.318 UBAP2L Zornitza Stark Gene: ubap2l has been classified as Green List (High Evidence).
Mendeliome v1.318 UBAP2L Zornitza Stark Classified gene: UBAP2L as Green List (high evidence)
Mendeliome v1.318 UBAP2L Zornitza Stark Gene: ubap2l has been classified as Green List (High Evidence).
Mendeliome v1.317 UBAP2L Zornitza Stark gene: UBAP2L was added
gene: UBAP2L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBAP2L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBAP2L were set to 35977029
Phenotypes for gene: UBAP2L were set to Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related
Review for gene: UBAP2L was set to GREEN
Added comment: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1).
Sources: Literature
Mendeliome v1.316 ALDH1A2 Zornitza Stark Phenotypes for gene: ALDH1A2 were changed from congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; dysmorphic features to Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025
Mendeliome v1.314 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Red List (Low Evidence).
Mendeliome v1.314 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Red List (low evidence)
Mendeliome v1.314 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Red List (Low Evidence).
Mendeliome v1.312 PDZD8 Zornitza Stark Gene: pdzd8 has been classified as Green List (High Evidence).
Mendeliome v1.312 PDZD8 Zornitza Stark Classified gene: PDZD8 as Green List (high evidence)
Mendeliome v1.312 PDZD8 Zornitza Stark Gene: pdzd8 has been classified as Green List (High Evidence).
Mendeliome v1.310 SLC31A1 Daniel Flanagan gene: SLC31A1 was added
gene: SLC31A1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC31A1 were set to PMID: 35913762
Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, SLC31A1-related (MONDO#0700092)
Review for gene: SLC31A1 was set to RED
Added comment: SLC31A1 is also referred to as CTR1.
Monozygotic twins with hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. Homozygous for a novel missense variant (p.(Arg95His)) in copper transporter CTR1, both parents heterozygous. A mouse knock-out model of CTR1 deficiency resulted in prenatal lethality.
Sources: Expert list
Mendeliome v1.308 TMEM163 Zornitza Stark Gene: tmem163 has been classified as Green List (High Evidence).
Mendeliome v1.307 TMEM163 Zornitza Stark Classified gene: TMEM163 as Green List (high evidence)
Mendeliome v1.307 TMEM163 Zornitza Stark Gene: tmem163 has been classified as Green List (High Evidence).
Mendeliome v1.306 NBAS Zornitza Stark Phenotypes for gene: NBAS were changed from Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800; Infantile liver failure syndrome 2, MIM# 616483 to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800; Infantile liver failure syndrome 2, MIM# 616483; Haemophagocytic lymphohistiocytosis (HLH), MONDO:0015541
Mendeliome v1.304 NBAS Zornitza Stark edited their review of gene: NBAS: Added comment: PMID 35902954 - Biallelic NBAS variants identifed in three HLH patients who harbored no pathogenic variants in any of the known HLH genes. Functionally, impaired NK-cell cytotoxicity and degranulation were revealed in both NBAS biallelic variant patients and in an NBAS-defcient NK-cell line. Knockdown of NBAS in an NK-cell line (IMC-1) using short hairpin RNA (shRNA) resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus.; Changed publications: 31761904, 35902954; Changed phenotypes: Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800, Infantile liver failure syndrome 2, MIM# 616483, Haemophagocytic lymphohistiocytosis (HLH), MONDO:0015541
Mendeliome v1.304 TYMS Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence).
Mendeliome v1.304 TYMS Zornitza Stark Classified gene: TYMS as Amber List (moderate evidence)
Mendeliome v1.304 TYMS Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence).
Mendeliome v1.303 TYMS Zornitza Stark reviewed gene: TYMS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita MONDO:0015780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.303 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mendeliome v1.303 COX11 Zornitza Stark Classified gene: COX11 as Green List (high evidence)
Mendeliome v1.303 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mendeliome v1.300 TMEM147 Zornitza Stark Gene: tmem147 has been classified as Green List (High Evidence).
Mendeliome v1.300 TMEM147 Zornitza Stark Classified gene: TMEM147 as Green List (high evidence)
Mendeliome v1.300 TMEM147 Zornitza Stark Gene: tmem147 has been classified as Green List (High Evidence).
Mendeliome v1.299 SAT1 Zornitza Stark Phenotypes for gene: SAT1 were changed from to Systemic lupus erythematosus, MONDO:0007915, SAT1-related; Keratosis follicularis spinulosa decalvans
Mendeliome v1.296 SAT1 Zornitza Stark Classified gene: SAT1 as Amber List (moderate evidence)
Mendeliome v1.296 SAT1 Zornitza Stark Gene: sat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.293 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835 to Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835; Diamond-Blackfan anemia (MONDO:0015253)
Mendeliome v1.291 GATA1 Zornitza Stark edited their review of gene: GATA1: Added comment: PMID 36029112: De novo GATA1 initiation codon variant (c.3G>A) identified in a Diamond-Blackfan Anaemia patient. Functional evidence showed that the variant does not affect the GATA1 mRNA but brings about a shorter GATA1 isoform (GATA1s) and reduced full-length functional GATA1 protein (GATA1fl), thereby contributing to an erythropoietic defect. Four other GATA1 variants (c.2T>C, c.220G>C, c.220delG, c.220+2T>C) found in eight families have been described as DBA phenotype.; Changed publications: 36029112; Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083, Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835, Diamond-Blackfan anemia (MONDO:0015253)
Mendeliome v1.291 LGI3 Zornitza Stark Gene: lgi3 has been classified as Green List (High Evidence).
Mendeliome v1.290 LGI3 Zornitza Stark Classified gene: LGI3 as Green List (high evidence)
Mendeliome v1.290 LGI3 Zornitza Stark Gene: lgi3 has been classified as Green List (High Evidence).
Mendeliome v1.289 TMEM147 Naomi Baker gene: TMEM147 was added
gene: TMEM147 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM147 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM147 were set to PMID: 36044892
Phenotypes for gene: TMEM147 were set to Neurodevelopmental disorder (MONDO:0700092), TMEM147-related
Review for gene: TMEM147 was set to GREEN
Added comment: PMID: 36044892; Twelve different variants reported in 23 affected individuals from 15 unrelated families with biallelic variants. All individuals had global developmental delay and intellectual disability. Consistent facial dysmorphisms included coarse facies, prominent forehead, board depressed nasal root, tented mouth, long smooth philtrum, and low-set ears. In vitro studies of missense variants demonstrated accelerated protein degradation via the autophagy-lysosomal pathway, while analysis of primary fibroblasts and granulocytes provided functional evidence of ER and nuclear envelope dysfunction.
Sources: Literature
Mendeliome v1.289 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Mendeliome v1.289 ADAMTS15 Zornitza Stark Classified gene: ADAMTS15 as Green List (high evidence)
Mendeliome v1.289 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Mendeliome v1.288 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Mendeliome v1.288 CAPRIN1 Zornitza Stark Classified gene: CAPRIN1 as Green List (high evidence)
Mendeliome v1.288 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Mendeliome v1.287 CBLB Alison Yeung Gene: cblb has been classified as Green List (High Evidence).
Mendeliome v1.287 CBLB Alison Yeung Classified gene: CBLB as Green List (high evidence)
Mendeliome v1.287 CBLB Alison Yeung Gene: cblb has been classified as Green List (High Evidence).
Mendeliome v1.285 TYMS Lucy Spencer gene: TYMS was added
gene: TYMS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TYMS was set to Other
Publications for gene: TYMS were set to 35931051
Phenotypes for gene: TYMS were set to Dyskeratosis congenita MONDO:0015780
Review for gene: TYMS was set to RED
Added comment: 8 families with dyskeratosis congenita and heterozygous variants in TYMS. 4 PTCs, 2 missense and 1 splice (2 families had the same frameshift). However in all families 1 unaffected parent was also heterozygous for the same TYSM variant.

The other parent in 3 of these families was then shown to carry a heterozygous variant in ENOSF1 which each affected child was also heterozygous for. ENOSF1 has been shown to modify TYMS expression at the RNA level by acting as an antisense molecule to TYMS. ENOSF1 partially overlaps TYMS on chromosome 18 and is transcribed in the opposite direction to TYMS. This paper is suggesting digenic inheritance.

The TYMS wild type parent from another family was seen to have a TYMSOS variant which was also observed along with the TYMS variant in their 2 affected children.

Immunoblotting showed a stark reduction in TYMS protein level in the cells of affected probands when compared to the parent carrier, wild-type parent, and the controls.

Lymphoblastoid cells from affected probands have severe TYMS deficiency, altered cellular deoxyribonucleotide triphosphate pools, and hypersensitivity to the TYMS-specific inhibitor 5-fluorouracil. These defects in the nucleotide metabolism pathway resulted in genotoxic stress, defective transcription, and abnormal telomere maintenance. Gene-rescue studies in cells from affected probands revealed that post-transcriptional epistatic silencing of TYMS is occurring via elevated ENOSF1.
Sources: Literature
Mendeliome v1.285 MET Zornitza Stark Phenotypes for gene: MET were changed from 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
Mendeliome v1.283 MET Zornitza Stark changed review comment from: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.; to: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.

AMBER for this association
Mendeliome v1.283 MET Zornitza Stark edited their review of gene: MET: Added comment: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.; Changed publications: 30777867
Mendeliome v1.283 LGI3 Melanie Marty gene: LGI3 was added
gene: LGI3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LGI3 were set to PMID: 35948005
Phenotypes for gene: LGI3 were set to Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi
Review for gene: LGI3 was set to GREEN
Added comment: Sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3.
Lgi3-null mice showed reduced and mis-local-ized Kv1 channel complexes in myelinated peripheral axons.
Sources: Literature
Mendeliome v1.280 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.280 BUD13 Alison Yeung Classified gene: BUD13 as Amber List (moderate evidence)
Mendeliome v1.280 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.279 BUD13 Alison Yeung gene: BUD13 was added
gene: BUD13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BUD13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUD13 were set to 35670808
Phenotypes for gene: BUD13 were set to Lipodystrophy, MONDO:0006573
Review for gene: BUD13 was set to AMBER
Added comment: 5 individuals with a lipodystrophy phenotype with a typical facial appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Although 3 individuals showed stunted growth, intellectual disability, and died within the first decade of life, 2 are adults with normal intellectual development. All individuals harbored an identical homozygous nonsense variant affecting the retention and splicing complex component BUD13. Individuals from only two Algerian families.
Sources: Literature
Mendeliome v1.276 ADAMTS15 Naomi Baker changed review comment from: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature; to: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature
Mendeliome v1.276 ADAMTS15 Naomi Baker gene: ADAMTS15 was added
gene: ADAMTS15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS15 were set to PMID: 35962790
Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related
Review for gene: ADAMTS15 was set to GREEN
Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature
Mendeliome v1.275 LEF1 Zornitza Stark Phenotypes for gene: LEF1 were changed from Ectodermal dysplasia, no OMIM# yet to Syndromic disease, MONDO:0002254, LEF1-related
Mendeliome v1.272 LEF1 Zornitza Stark Classified gene: LEF1 as Green List (high evidence)
Mendeliome v1.272 LEF1 Zornitza Stark Gene: lef1 has been classified as Green List (High Evidence).
Mendeliome v1.271 LEF1 Zornitza Stark edited their review of gene: LEF1: Added comment: Monoallelic variants in LEF1 reported in 11 affected individuals from 4 unrelated families, and a biallelic variant reported in an affected individual from a consanguineous family. The phenotypic spectrum included various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Haploinsufficiency or loss of DNA binding postulated to be responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants postulated to be associated with a severe phenotype.; Changed rating: GREEN; Changed publications: 32022899, 35583550; Changed phenotypes: Syndromic disease, MONDO:0002254, LEF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.271 REEP1 Zornitza Stark Phenotypes for gene: REEP1 were changed from Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250; Charcot-Marie-Tooth; severe congenital distal SMA with diaphragmatic paralysis; congenital axonal neuropathy and diaphragmatic palsy to Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011; Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250
Mendeliome v1.270 REEP1 Zornitza Stark reviewed gene: REEP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.270 CCDC82 Zornitza Stark Gene: ccdc82 has been classified as Green List (High Evidence).
Mendeliome v1.270 CCDC82 Zornitza Stark Phenotypes for gene: CCDC82 were changed from Intellectual disability and spastic paraparesis, no OMIM # to Neurodevelopmental disorder, MONDO:0700092, CCDC82-related
Mendeliome v1.268 NPNT Zornitza Stark Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.268 NPNT Zornitza Stark Phenotypes for gene: NPNT were changed from Renal agenesis, no OMIM # to Renal agenesis, MONDO:0018470, NPNT-related
Mendeliome v1.266 NPNT Zornitza Stark reviewed gene: NPNT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal agenesis, MONDO:0018470, NPNT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.266 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Skeletal dysplasia, MONDO:0018230 to Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia
Mendeliome v1.265 KIF5B Zornitza Stark Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.265 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Kyphomelic dysplasia, no OMIM # to Skeletal dysplasia, MONDO:0018230
Mendeliome v1.264 KIF5B Zornitza Stark reviewed gene: KIF5B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia, MONDO:0018230; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.264 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome AR; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD to Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome, type VI, MIM# 620022; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD
Mendeliome v1.263 COL9A3 Zornitza Stark edited their review of gene: COL9A3: Changed phenotypes: Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969, Stickler syndrome, type VI, MIM# 620022, Deafness
Mendeliome v1.263 LNPK Chirag Patel Classified gene: LNPK as Green List (high evidence)
Mendeliome v1.263 LNPK Chirag Patel Gene: lnpk has been classified as Green List (High Evidence).
Mendeliome v1.262 LNPK Chirag Patel reviewed gene: LNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35599435; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.262 CCDC82 Chirag Patel Classified gene: CCDC82 as Green List (high evidence)
Mendeliome v1.262 CCDC82 Chirag Patel Gene: ccdc82 has been classified as Green List (High Evidence).
Mendeliome v1.261 CCDC82 Chirag Patel gene: CCDC82 was added
gene: CCDC82 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC82 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Phenotypes for gene: CCDC82 were set to Intellectual disability and spastic paraparesis, no OMIM #
Review for gene: CCDC82 was set to GREEN
Added comment: 4 consanguineous families with 9 affected individuals with developmental delay/intellectual disability, and 2 families had spasticity and 1 had epilepsy. WES identified 3 homozgyous truncating variants, segregating with disease and parents as carriers. No functional studies.
Sources: Literature
Mendeliome v1.260 NPNT Chirag Patel Classified gene: NPNT as Green List (high evidence)
Mendeliome v1.260 NPNT Chirag Patel Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.260 NPNT Chirag Patel Classified gene: NPNT as Green List (high evidence)
Mendeliome v1.260 NPNT Chirag Patel Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.259 NPNT Chirag Patel gene: NPNT was added
gene: NPNT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Phenotypes for gene: NPNT were set to Renal agenesis, no OMIM #
Review for gene: NPNT was set to GREEN
Added comment: 3 consanguineous families with multiple affecteds with bilateral renal agenesis. Whole-exome sequencing (WES)-based homozygosity mapping identified 2 homozygous truncating variants. Reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Loss of nephronectin (NPNT) is known to lead to failure of metanephric kidney development with resulting renal agenesis in murine models.
Sources: Literature
Mendeliome v1.258 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Mendeliome v1.258 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.258 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Mendeliome v1.258 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.257 KIF5B Chirag Patel gene: KIF5B was added
gene: KIF5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to PMID: 35342932
Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM #
Review for gene: KIF5B was set to GREEN
Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants. Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages.
Sources: Literature
Mendeliome v1.256 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from neurodevelopmental disorder MONDO:0700092; FBXW7-related neurodevelopmental syndrome; Wilms tumor MONDO:0006058 to Developmental delay, hypotonia, and impaired language, MIM# 620012; Wilms tumour predisposition
Mendeliome v1.255 FBXW7 Zornitza Stark edited their review of gene: FBXW7: Changed phenotypes: Developmental delay, hypotonia, and impaired language, MIM# 620012, Wilms tumour predisposition
Mendeliome v1.254 ACADS Zornitza Stark Classified gene: ACADS as Amber List (moderate evidence)
Mendeliome v1.254 ACADS Zornitza Stark Gene: acads has been classified as Amber List (Moderate Evidence).
Mendeliome v1.253 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Mendeliome v1.253 FOCAD Zornitza Stark Classified gene: FOCAD as Green List (high evidence)
Mendeliome v1.253 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Mendeliome v1.252 FOCAD Zornitza Stark gene: FOCAD was added
gene: FOCAD was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOCAD were set to 35864190
Phenotypes for gene: FOCAD were set to Liver disease, severe congenital, MIM# 619991
Review for gene: FOCAD was set to GREEN
Added comment: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).
Sources: Expert Review
Mendeliome v1.249 TAF4 Zornitza Stark Classified gene: TAF4 as Green List (high evidence)
Mendeliome v1.249 TAF4 Zornitza Stark Gene: taf4 has been classified as Green List (High Evidence).
Mendeliome v1.248 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Mendeliome v1.248 ZMYND8 Zornitza Stark Classified gene: ZMYND8 as Green List (high evidence)
Mendeliome v1.248 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Mendeliome v1.247 ZMYND8 Zornitza Stark gene: ZMYND8 was added
gene: ZMYND8 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Review for gene: ZMYND8 was set to GREEN
Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565).

Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11).

As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression.

The protein is broadly expressed in brain and shows highest expression in early development.

Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain).

Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning.
Sources: Expert Review
Mendeliome v1.246 TRAC Seb Lunke Classified gene: TRAC as Amber List (moderate evidence)
Mendeliome v1.246 TRAC Seb Lunke Added comment: Comment on list classification: Single variant reported to date in 6 patients; 2 unrelated children from consanguineous families of Pakistani descent (PMID: 21206088); 1 non-consanguineous family from North-west India (PMID: 33909184) and 1 consanguineous parents of East Indian (https://lymphosign.com/doi/10.14785/lymphosign-2022-0001) Also note annotation issues in certain variant curation and annotation tools.
Mendeliome v1.246 TRAC Seb Lunke Gene: trac has been classified as Amber List (Moderate Evidence).
Mendeliome v1.241 SMG9 Zornitza Stark Phenotypes for gene: SMG9 were changed from Heart and brain malformation syndrome, MIM# 616920 to Heart and brain malformation syndrome, MIM# 616920; Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995
Mendeliome v1.239 SMG9 Zornitza Stark edited their review of gene: SMG9: Added comment: PMID 35087184: 5 individuals from 3 unrelated Finnish families reported with same homozygous missense variant (founder effect) and predominantly neurological phenotype. Uncertain if this is a distinct disorder or part of a spectrum with the previously reported cases.; Changed publications: 27018474, 31390136, 35087184; Changed phenotypes: Heart and brain malformation syndrome, MIM# 616920, Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995
Mendeliome v1.238 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Mendeliome v1.237 OTULIN Zornitza Stark edited their review of gene: OTULIN: Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Mendeliome v1.237 SPTBN5 Zornitza Stark Phenotypes for gene: SPTBN5 were changed from Sacral agenesis; congenital anomalies to Neurodevelopmental disorder, MONDO:0700092, SPTBN5-related; Sacral agenesis; congenital anomalies
Mendeliome v1.234 SPTBN5 Zornitza Stark Classified gene: SPTBN5 as Green List (high evidence)
Mendeliome v1.234 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Green List (High Evidence).
Mendeliome v1.233 SPTBN5 Zornitza Stark changed review comment from: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature; to: Bi-allelic variants: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature
Mendeliome v1.233 SPTBN5 Zornitza Stark edited their review of gene: SPTBN5: Added comment: Monoallelic variants:
- Four probands from unrelated families (1x Pakistani and 3x Italian) with de novo heterozygous SPTBN5 variants
- 3x missense variants and 1x LoF variant were reported
- Phenotypes include intellectual disability (mild to severe), aggressive tendencies and variable features such as craniofacial and physical dysmorphisms, autistic behavior, and gastroesophageal reflux; Changed rating: GREEN; Changed publications: 35782384, 32732226, 28007035; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SPTBN5-related, Sacral agenesis, congenital anomalies; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.231 CPS1 Zornitza Stark reviewed gene: CPS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Pulmonary hypertension, neonatal, susceptibility to} 615371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.231 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099 to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related
Mendeliome v1.228 OTULIN Zornitza Stark edited their review of gene: OTULIN: Added comment: PMID 35587511: Multiple individuals reported with haploinsufficiency of OTULIN and severe staphylococcal disease, with life-threatening skin or pulmonary necrosis. Functional data.; Changed publications: 27523608, 27559085, 35587511; Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Susceptibility to infection with Staphylococcus aureus, Hereditary predisposition to infections, MONDO:0015979, OTULIN-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.228 NOX1 Zornitza Stark gene: NOX1 was added
gene: NOX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NOX1 were set to 29091079; 32064493
Phenotypes for gene: NOX1 were set to Inflammatory bowel disease, MONDO:0005265, NOX1-related
Review for gene: NOX1 was set to AMBER
Added comment: 8 IBD patients with early onset of IBD with progressive and severe colonic disease, refractory to conventional therapy and functional studies suggesting variant-dependent loss of NOX1-mediated superoxide generation. However, high frequency of nonsynonymous mutations in NOX1 suggests that NOX1 is not a highly penetrant Mendelian disorder and that other genetic modifiers or environmental factors may contribute to disease pathogenesis.

The variant reported in PMID 32064493 is present in 6 hets in gnomad.
Sources: Literature
Mendeliome v1.223 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Mendeliome v1.223 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Mendeliome v1.223 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Mendeliome v1.222 SARS Ain Roesley Classified gene: SARS as Green List (high evidence)
Mendeliome v1.222 SARS Ain Roesley Gene: sars has been classified as Green List (High Evidence).
Mendeliome v1.221 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Mendeliome v1.219 PSMC1 Zornitza Stark Classified gene: PSMC1 as Red List (low evidence)
Mendeliome v1.219 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Mendeliome v1.218 PSMC1 Zornitza Stark commented on gene: PSMC1: Single family only, homozygous missense variant.
Mendeliome v1.217 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Mendeliome v1.216 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Mendeliome v1.216 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Mendeliome v1.213 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Mendeliome v1.213 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Mendeliome v1.213 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Mendeliome v1.212 PSMC1 Hazel Phillimore gene: PSMC1 was added
gene: PSMC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC1 were set to PMID: 35861243
Phenotypes for gene: PSMC1 were set to spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes
Mode of pathogenicity for gene: PSMC1 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: PSMC1 was set to AMBER
Added comment: Homozygosity mapping on one large consanguineous Bedouin kindred showed three affected children (out of the ten) to be homozygous for NM_002802.3:c.983T>C; p.(Ile328Thr).

Drosophila rescue experiments were carried out. Transgenic studies using drosophila with the silenced ortholog Rpt2 gene were rescued by the human wild-type PSMC1.

Three of the ten offspring of healthy consanguineous parents of Bedouin Israeli ancestry were affected with a similar phenotype of failure to thrive, developmental delay and severe intellectual disability, spastic tetraplegia with central hypotonia, chorea, as well as hearing loss. None of the three achieved verbal communication or ambulation (sitting / standing) at any age. They had mild dysmorphism of borderline dolichocephaly and microcephaly, prominent bushy eyebrows, flat midface, long nasal bridge and micrognathia. All three had micropenis with undescended testes. One of the affected (as a toddler) underwent thorough endocrinological analysis: testosterone and gonadotropin levels were low.
Sources: Literature
Mendeliome v1.212 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to GREEN
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Mendeliome v1.212 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.212 BMP3 Seb Lunke Classified gene: BMP3 as Amber List (moderate evidence)
Mendeliome v1.212 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.211 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Review for gene: BMP3 was set to AMBER
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD. Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive
Sources: Literature
Mendeliome v1.210 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Mendeliome v1.210 C18orf32 Alison Yeung Classified gene: C18orf32 as Red List (low evidence)
Mendeliome v1.210 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Mendeliome v1.209 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.209 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Mendeliome v1.209 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.208 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Cystic renal disease MONDO:0002473, ALG5-related, Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Mendeliome v1.208 SLITRK2 Paul De Fazio gene: SLITRK2 was added
gene: SLITRK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLITRK2 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: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092
Review for gene: SLITRK2 was set to GREEN
gene: SLITRK2 was marked as current diagnostic
Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients).

The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother.

Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait.
Sources: Literature
Mendeliome v1.207 RFC1 Ain Roesley Classified gene: RFC1 as Amber List (moderate evidence)
Mendeliome v1.207 RFC1 Ain Roesley Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.206 C18orf32 Naomi Baker gene: C18orf32 was added
gene: C18orf32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C18orf32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C18orf32 were set to PMID:35107634
Phenotypes for gene: C18orf32 were set to Neurodevelopmental disorder (MONDO:0700092), C18orf32-related
Review for gene: C18orf32 was set to RED
Added comment: Two siblings reported as affected, although sequencing only performed in one sibling, with homozygous loss-of-function variant identified. Clinical presentation included developmental delay, recurrent lower respiratory tract infections, sparse rough hair, roving eye movements, hypotonia, bilateral ankle contractures and inverted nipples.
Sources: Literature
Mendeliome v1.206 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Mendeliome v1.206 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.205 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Mendeliome v1.205 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.204 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Red List (Low Evidence).
Mendeliome v1.204 ADGRL1 Elena Savva gene: ADGRL1 was added
gene: ADGRL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADGRL1 were set to PMID: 35907405
Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092)
Review for gene: ADGRL1 was set to GREEN
Added comment: PMID: 35907405 - 9 patients w/ ADHD (3/9), autism (4/9), mild-moderate ID (5/9) and epilepsy (2/9) and facial dysmorphism (7/9). Variants include missense (4) and PTCs (5), and were either de novo (7/9) or inherited from parents with learning difficulties/ID (2/9).

Functional studies on both PTCs and missense variants show significant reductions in calcium signalling and surface protein.

Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable.
Sources: Literature
Mendeliome v1.203 EHHADH Zornitza Stark Classified gene: EHHADH as Amber List (moderate evidence)
Mendeliome v1.203 EHHADH Zornitza Stark Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Mendeliome v1.202 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from Thyroid dyshormonogenesis 6 - MIM#607200 to Thyroid dyshormonogenesis 6 - MIM#607200; Inflammatory bowel disease, MONDO:0005265, DUOX2-related
Mendeliome v1.199 DUOX2 Zornitza Stark Classified gene: DUOX2 as Amber List (moderate evidence)
Mendeliome v1.199 DUOX2 Zornitza Stark Gene: duox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.198 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Mendeliome v1.197 CWH43 Zornitza Stark Classified gene: CWH43 as Red List (low evidence)
Mendeliome v1.197 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Mendeliome v1.196 ADGRA3 Zornitza Stark Gene: adgra3 has been classified as Red List (Low Evidence).
Mendeliome v1.196 ADGRA3 Zornitza Stark gene: ADGRA3 was added
gene: ADGRA3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ADGRA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGRA3 were set to 23105016
Phenotypes for gene: ADGRA3 were set to Retinitis pigmentosa, MONDO:0019200, ADGRA3-related
Review for gene: ADGRA3 was set to RED
Added comment: Only one report of a missense that is a VUS identified as a candidate through autozygome analysis (PMID: 23105016)
Sources: Expert Review
Mendeliome v1.191 ROBO4 Zornitza Stark Classified gene: ROBO4 as Amber List (moderate evidence)
Mendeliome v1.191 ROBO4 Zornitza Stark Gene: robo4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.186 MCM10 Zornitza Stark Classified gene: MCM10 as Amber List (moderate evidence)
Mendeliome v1.186 MCM10 Zornitza Stark Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.183 IKZF1 Zornitza Stark edited their review of gene: IKZF1: Added comment: PMID 35333544: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects reported. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.; Changed publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317, 35333544; Changed phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset, Immune dysregulation
Mendeliome v1.180 TMEM63C Zornitza Stark Gene: tmem63c has been classified as Green List (High Evidence).
Mendeliome v1.180 TMEM63C Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966
Mendeliome v1.179 TMEM63C Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.179 EIF2B1 Elena Savva reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31882561; Phenotypes: Leukoencephalopathy with vanishing white matter MIM#603896, permanent neonatal/early onset diabetes and transient liver dysfunction; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.176 WASL Zornitza Stark Gene: wasl has been classified as Red List (Low Evidence).
Mendeliome v1.176 WASL Zornitza Stark gene: WASL was added
gene: WASL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASL were set to 33571872
Phenotypes for gene: WASL were set to Parkinson's disease, MONDO:0005180, WASL-related
Review for gene: WASL was set to RED
Added comment: Single family reported, where bi-allelic variants segregated with PD in three affected individuals.
Sources: Literature
Mendeliome v1.173 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Association with HIPKD:
Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts. Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.; Changed publications: 28108845, 28373276, 32595772; Changed phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065), Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Mendeliome v1.173 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441 to Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related
Mendeliome v1.171 SLCO2A1 Zornitza Stark edited their review of gene: SLCO2A1: Added comment: PMID 29313109: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology. Some overlap with the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.; Changed publications: 23509104, 27134495, 33852188, 22331663, 27134495, 29313109; Changed phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441, Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related
Mendeliome v1.169 C20orf24 Zornitza Stark Gene: c20orf24 has been classified as Red List (Low Evidence).
Mendeliome v1.166 IL23R Zornitza Stark Classified gene: IL23R as Amber List (moderate evidence)
Mendeliome v1.166 IL23R Zornitza Stark Gene: il23r has been classified as Amber List (Moderate Evidence).
Mendeliome v1.165 HYOU1 Zornitza Stark Classified gene: HYOU1 as Amber List (moderate evidence)
Mendeliome v1.165 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.162 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Mendeliome v1.162 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Mendeliome v1.162 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Mendeliome v1.160 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Mendeliome v1.159 C9orf84 Zornitza Stark Gene: c9orf84 has been classified as Green List (High Evidence).
Mendeliome v1.159 C9orf84 Zornitza Stark Classified gene: C9orf84 as Green List (high evidence)
Mendeliome v1.159 C9orf84 Zornitza Stark Gene: c9orf84 has been classified as Green List (High Evidence).
Mendeliome v1.155 LMAN2L Zornitza Stark Phenotypes for gene: LMAN2L were changed from Mental retardation, autosomal recessive, 52; OMIM #616887 to Mental retardation, autosomal recessive, 52 OMIM #616887; Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Mendeliome v1.154 LMAN2L Zornitza Stark edited their review of gene: LMAN2L: Changed phenotypes: Mental retardation, autosomal recessive, 52 OMIM #616887, Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Mendeliome v1.154 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929, Attention deficit-hyperactivity disorder 8 , MIM# 619957
Mendeliome v1.154 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929 to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929; Attention deficit-hyperactivity disorder 8 , MIM# 619957
Mendeliome v1.152 CDH2 Zornitza Stark edited their review of gene: CDH2: Added comment: PMID 34702855: three sibs with homozygous missense and strikingly severe ADHD. Mouse model of same variant recapitulated the phenotype. AMBER for bi-allelic association (segregation and functional data).; Changed publications: 31585109, 34702855; Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929:Attention deficit-hyperactivity disorder 8 , MIM# 619957; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.149 KITLG Zornitza Stark Classified gene: KITLG as Green List (high evidence)
Mendeliome v1.149 KITLG Zornitza Stark Gene: kitlg has been classified as Green List (High Evidence).
Mendeliome v1.148 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.148 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Mendeliome v1.148 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.147 CLDN5 Zornitza Stark gene: CLDN5 was added
gene: CLDN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia, MONDO:0016210, CLDN5-related
Mode of pathogenicity for gene: CLDN5 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: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).

One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting. The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.

CT scans of both showed brain calcifications and aberrant blood flow patterns. Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Mendeliome v1.144 PSMB9 Zornitza Stark Classified gene: PSMB9 as Green List (high evidence)
Mendeliome v1.144 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Green List (High Evidence).
Mendeliome v1.143 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.143 HCK Zornitza Stark Classified gene: HCK as Amber List (moderate evidence)
Mendeliome v1.143 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.142 HCK Zornitza Stark gene: HCK was added
gene: HCK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HCK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCK were set to 34536415
Phenotypes for gene: HCK were set to Autoinflammatory syndrome, MONDO:0019751, HCK-related
Mode of pathogenicity for gene: HCK was set to Other
Review for gene: HCK was set to AMBER
Added comment: Single patient with supportive functional data.
Sources: Literature
Mendeliome v1.141 TBX21 Zornitza Stark Classified gene: TBX21 as Amber List (moderate evidence)
Mendeliome v1.141 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.140 TBX21 Zornitza Stark changed review comment from: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified.

Association with asthma and nasal polyps pertains to promoter SNPs.; to: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified. Functional data.

Association with asthma and nasal polyps pertains to promoter SNPs.
Mendeliome v1.139 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Mendeliome v1.139 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Mendeliome v1.138 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Mendeliome v1.138 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Mendeliome v1.138 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Mendeliome v1.137 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.137 PIK3C2B Zornitza Stark Classified gene: PIK3C2B as Amber List (moderate evidence)
Mendeliome v1.137 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.136 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Mendeliome v1.135 CCDC155 Zornitza Stark Classified gene: CCDC155 as Green List (high evidence)
Mendeliome v1.135 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Mendeliome v1.134 CCDC155 Melanie Marty gene: CCDC155 was added
gene: CCDC155 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC155 were set to 35674372; 35708642; 29790874; 35587281
Phenotypes for gene: CCDC155 were set to Non-obstructive azoospermia; Premature ovarian insufficiency
Review for gene: CCDC155 was set to GREEN
Added comment: Current HGNC name is KASH5

Summary: 4 families reported with non-obstructive azoospermia or premature ovarian insufficiency. Functional studies have been performed and mouse models recapitulate the phenotype.

PMID: 35674372 CNV and frameshift variants in KASH5 were identified in a non-obstructive azoospermia affected patient and in his infertile sister by whole-exome sequencing and CNV array. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis.

PMID: 35708642 Hom splice identified in KASH5 in 2 sisters with premature ovarian insufficiency. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes.

PMID: 29790874 2 brothers with non-obstructive azoospermia with hom missense in CCDC155

35587281 2 siblings with hom missense in CCDC155 non-obstructive azoospermia and premature ovarian insufficiency.
Sources: Literature
Mendeliome v1.134 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.134 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Mendeliome v1.134 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.133 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Traboulsi syndrome , MIM#601552 to Traboulsi syndrome , MIM#601552; Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Mendeliome v1.130 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Mendeliome v1.130 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.130 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Mendeliome v1.130 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.129 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Mendeliome v1.129 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Mendeliome v1.129 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Mendeliome v1.128 PABPC1 Elena Savva gene: PABPC1 was added
gene: PABPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PABPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PABPC1 were set to PMID: 35511136
Phenotypes for gene: PABPC1 were set to Neurodevelopmental disorder, PABPC1-related (MONDO#0700092)
Review for gene: PABPC1 was set to GREEN
Added comment: PMID: 35511136 - 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1.
Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not.
Sources: Literature
Mendeliome v1.127 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Mendeliome v1.127 WNK3 Zornitza Stark Classified gene: WNK3 as Green List (high evidence)
Mendeliome v1.127 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Mendeliome v1.126 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Mendeliome v1.126 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Mendeliome v1.126 WNT7B Zornitza Stark Classified gene: WNT7B as Green List (high evidence)
Mendeliome v1.126 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Mendeliome v1.125 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to GREEN
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model.
Sources: Literature
Mendeliome v1.124 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Mendeliome v1.124 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Mendeliome v1.123 TMEM63C Elena Savva gene: TMEM63C was added
gene: TMEM63C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM63C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM63C were set to PMID: 35718349
Phenotypes for gene: TMEM63C were set to Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related
Review for gene: TMEM63C was set to GREEN
Added comment: PMID: 35718349 - Four NMD PTCs observed in at least 3 unrelated patients. Two segregated strongly in highly consanguineous families.
Common clinical details include mild ID, spastic paraplegia, hypereflexia, spasticity, delayed motor development. Single patient was microcephalic
Sources: Literature
Mendeliome v1.122 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.122 MAL Zornitza Stark Classified gene: MAL as Amber List (moderate evidence)
Mendeliome v1.122 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.121 MAL Zornitza Stark gene: MAL was added
gene: MAL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAL were set to 35217805
Phenotypes for gene: MAL were set to Leukodystrophy MONDO:0019046, MAL-related
Review for gene: MAL was set to AMBER
Added comment: Single family with two affected siblings reported, with homozygous missense variant, some functional data.
Sources: Literature
Mendeliome v1.119 TAF8 Zornitza Stark changed review comment from: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature; to: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. Unclear if this is a founder variant, families of different ethnicities. One family with different compound heterozygous variants.
Sources: Literature
Mendeliome v1.119 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Mendeliome v1.119 TAF8 Zornitza Stark Classified gene: TAF8 as Green List (high evidence)
Mendeliome v1.119 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Mendeliome v1.118 TAF8 Zornitza Stark gene: TAF8 was added
gene: TAF8 was added to Mendeliome. Sources: Literature
founder tags were added to gene: TAF8.
Mode of inheritance for gene: TAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF8 were set to 29648665; 35759269
Phenotypes for gene: TAF8 were set to Neurodevelopmental disorder, MONDO:0700092, TAF8-related
Review for gene: TAF8 was set to GREEN
Added comment: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature
Mendeliome v1.117 PNPT1 Zornitza Stark Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934) to Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934); Spinocerebellar ataxia 25, MIM# 608703
Mendeliome v1.114 TTC25 Arina Puzriakova reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486780, 31765523, 33715250, 33746037, 34215651; Phenotypes: Ciliary dyskinesia, primary, 35, OMIM:617092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.114 CXCR2 Zornitza Stark Classified gene: CXCR2 as Green List (high evidence)
Mendeliome v1.114 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Green List (High Evidence).
Mendeliome v1.113 RHOG Zornitza Stark Gene: rhog has been classified as Amber List (Moderate Evidence).
Mendeliome v1.113 RHOG Zornitza Stark Classified gene: RHOG as Amber List (moderate evidence)
Mendeliome v1.113 RHOG Zornitza Stark Gene: rhog has been classified as Amber List (Moderate Evidence).
Mendeliome v1.112 RHOG Zornitza Stark gene: RHOG was added
gene: RHOG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RHOG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RHOG were set to 33513601
Phenotypes for gene: RHOG were set to Genetic HLH, MONDO:0015541, RHOG-related
Review for gene: RHOG was set to AMBER
Added comment: Single individual reported, extensive functional data supports gene-disease association.
Sources: Literature
Mendeliome v1.111 TNFSF13 Zornitza Stark Gene: tnfsf13 has been classified as Red List (Low Evidence).
Mendeliome v1.111 TNFSF13 Zornitza Stark gene: TNFSF13 was added
gene: TNFSF13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNFSF13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFSF13 were set to 32298700
Phenotypes for gene: TNFSF13 were set to Hypogammaglobulinaemia, MONDO:0015977, TNSF13-related
Review for gene: TNFSF13 was set to RED
Added comment: Single individual, consanguineous parents.
Sources: Literature
Mendeliome v1.110 POU2AF1 Zornitza Stark Gene: pou2af1 has been classified as Red List (Low Evidence).
Mendeliome v1.110 POU2AF1 Zornitza Stark gene: POU2AF1 was added
gene: POU2AF1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: POU2AF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POU2AF1 were set to 33571536
Phenotypes for gene: POU2AF1 were set to Agammaglobulinaemia, MONDO:0015977, POU2AF1-related
Review for gene: POU2AF1 was set to RED
Added comment: Single individual from consanguineous parents lacking immunoglobulins despite normal total B-cell numbers.
Sources: Expert Review
Mendeliome v1.109 CD28 Zornitza Stark Gene: cd28 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.109 CD28 Zornitza Stark Classified gene: CD28 as Amber List (moderate evidence)
Mendeliome v1.109 CD28 Zornitza Stark Gene: cd28 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.108 CD28 Zornitza Stark changed review comment from: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data.
Sources: Expert Review; to: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1.
Sources: Expert Review
Mendeliome v1.108 CD28 Zornitza Stark gene: CD28 was added
gene: CD28 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CD28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD28 were set to 34214472
Phenotypes for gene: CD28 were set to Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs
Review for gene: CD28 was set to RED
Added comment: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data.
Sources: Expert Review
Mendeliome v1.107 IKZF3 Zornitza Stark Classified gene: IKZF3 as Green List (high evidence)
Mendeliome v1.107 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Green List (High Evidence).
Mendeliome v1.106 COPG1 Zornitza Stark Gene: copg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.106 COPG1 Zornitza Stark Classified gene: COPG1 as Amber List (moderate evidence)
Mendeliome v1.106 COPG1 Zornitza Stark Gene: copg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.105 COPG1 Zornitza Stark gene: COPG1 was added
gene: COPG1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: COPG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPG1 were set to 33529166
Phenotypes for gene: COPG1 were set to Combined immunodeficiency MONDO:0015131, COPG1-related
Review for gene: COPG1 was set to RED
Added comment: Five Omani siblings, born to consanguineous parents, homozygous missense.

Homozygous Copg1K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice.
Sources: Expert Review
Mendeliome v1.103 IFNAR2 Zornitza Stark Classified gene: IFNAR2 as Green List (high evidence)
Mendeliome v1.103 IFNAR2 Zornitza Stark Gene: ifnar2 has been classified as Green List (High Evidence).
Mendeliome v1.102 IFNAR2 Zornitza Stark edited their review of gene: IFNAR2: Added comment: Five children from Greenland, Canada, and Alaska presenting with viral diseases, including life-threatening COVID-19 or influenza, in addition to meningoencephalitis and/or hemophagocytic lymphohistiocytosis following live-attenuated viral vaccination; Changed rating: GREEN; Changed publications: 26424569, 35442417
Mendeliome v1.100 IFNAR1 Zornitza Stark Classified gene: IFNAR1 as Green List (high evidence)
Mendeliome v1.100 IFNAR1 Zornitza Stark Gene: ifnar1 has been classified as Green List (High Evidence).
Mendeliome v1.99 SLC26A1 Zornitza Stark Classified gene: SLC26A1 as Red List (low evidence)
Mendeliome v1.99 SLC26A1 Zornitza Stark Gene: slc26a1 has been classified as Red List (Low Evidence).
Mendeliome v1.98 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174 to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant
Mendeliome v1.96 NEK8 Zornitza Stark edited their review of gene: NEK8: Added comment: ESHG 2022: 12 families with paediatric renal cystic disease (enlarged kidneys, kidney cysts, ESKF <20yrs) -3 recurrent HTZ variants in NEK8 kinase domain (Arg45Trp, Ile150Met, Lys157Gln) -suspected dominant negative effect -patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8 (Note carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF); Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Familial renal cystic disease MONDO:0019741, NEK8-related, dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.96 DRD2 Zornitza Stark Phenotypes for gene: DRD2 were changed from to Combined dystonia, MONDO:0020065, DRD2-related; dystonia; chorea; anxiety; ataxia; orofacial dyskinesia; tremor; memory problems
Mendeliome v1.93 DRD2 Zornitza Stark reviewed gene: DRD2: Rating: RED; Mode of pathogenicity: Other; Publications: 33200438; Phenotypes: Combined dystonia, MONDO:0020065, DRD2-related, dystonia, chorea, anxiety, ataxia, orofacial dyskinesia, tremor, memory problems; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.91 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Mendeliome v1.91 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Mendeliome v1.91 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Mendeliome v1.91 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Mendeliome v1.89 SLC26A1 Krithika Murali reviewed gene: SLC26A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Nephrolithiasis, calcium oxalate - MIM#167030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.89 DDR2 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are associated with a severe perinatal skeletal dysplasia.

Mono-allelic variants cause Warburg-Cinotti syndrome, which is characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acroosteolysis. Four unrelated families reported with missense variants, which were activating.; to: Bi-allelic variants in this gene are associated with a severe perinatal skeletal dysplasia. LoF.

Mono-allelic variants cause Warburg-Cinotti syndrome, which is characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acroosteolysis. Four unrelated families reported with missense variants, which were activating. GoF.
Mendeliome v1.85 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 67, MIM# 619927, Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Mendeliome v1.85 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, MIM# 619927 to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927; Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Mendeliome v1.82 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Added comment: Single individual reported with bi-allelic LoF variant. RED/AMBER for bi-allelic variants.; Changed publications: 28628100, 23033978, 26350204, 24896178, 35675825; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.79 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230 to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Hereditary spastic paraplegia MONDO:0019064, GCH1-related
Mendeliome v1.77 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed phenotypes: Hyper-IgE recurrent infection syndrome 4A, autosomal dominant , MIM#619752, Hyper-IgE recurrent infection syndrome 4B, autosomal recessive, MIM# 618523, Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant, Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Mendeliome v1.76 KCNA5 Zornitza Stark Classified gene: KCNA5 as Amber List (moderate evidence)
Mendeliome v1.76 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.75 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367 to Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835
Mendeliome v1.74 GATA1 Zornitza Stark edited their review of gene: GATA1: Added comment: Variants in GATA1 are associated with a number of haematological disorders, which probably represent a spectrum rather than distinct entities.; Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083, Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835
Mendeliome v1.74 NR4A2 Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual disability; epilepsy to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Mendeliome v1.73 NR4A2 Zornitza Stark edited their review of gene: NR4A2: Changed phenotypes: Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Mendeliome v1.71 KCNC2 Zornitza Stark Classified gene: KCNC2 as Green List (high evidence)
Mendeliome v1.71 KCNC2 Zornitza Stark Gene: kcnc2 has been classified as Green List (High Evidence).
Mendeliome v1.68 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Chorioretinal atrophy, progressive bifocal, MIM# 600790; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761 to Chorioretinal atrophy, progressive bifocal, MIM# 600790; Pontocerebellar hypoplasia, type 17, MIM# 619909; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976
Mendeliome v1.66 PRDM13 Zornitza Stark edited their review of gene: PRDM13: Added comment: Note only single family reported with Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976 -- this likely lies on the same spectrum as Pontocerebellar hypoplasia, type 17, MIM# 619909 rather than being a distinct disorder.; Changed publications: 30710461, 34730112; Changed phenotypes: Retinal dystrophy, Chorioretinal atrophy, progressive bifocal, MIM# 600790, Pontocerebellar hypoplasia, type 17, MIM# 619909, Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.65 RBFOX2 Chern Lim changed review comment from: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.; to: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (1x nonsense, 1x frameshift, 1x canonical splice variants). All 3 probands have hypoplastic left heart syndrome (HLHS) and no extra-cardiac features. Same cohort later included in PMID: 32368696, listed one additional de novo variant in this gene (missense variant) in a patient with conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Mendeliome v1.63 SLC5A6 Zornitza Stark Phenotypes for gene: SLC5A6 were changed from Developmental delay; epilepsy; neurodegeneration; Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973 to Peripheral motor neuropathy, childhood-onset, biotin-responsive, MIM# 619903; Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Mendeliome v1.61 SLC5A6 Zornitza Stark edited their review of gene: SLC5A6: Added comment: PMID 35013551: 5 individuals from 3 unrelated families reported with predominantly neuropathy phenotype.; Changed publications: 31754459, 27904971, 35013551; Changed phenotypes: Peripheral motor neuropathy, childhood-onset, biotin-responsive, MIM# 619903, Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Mendeliome v1.60 BUB1 Elena Savva Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.60 BUB1 Elena Savva Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.59 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.59 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.56 BUB1 Elena Savva Classified gene: BUB1 as Red List (low evidence)
Mendeliome v1.56 BUB1 Elena Savva Gene: bub1 has been classified as Red List (Low Evidence).
Mendeliome v1.53 BUB1 Elena Savva Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.53 BUB1 Elena Savva Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.52 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.52 BUB1 Zornitza Stark Gene: bub1 has been classified as Green List (High Evidence).
Mendeliome v1.52 RRM1 Seb Lunke Classified gene: RRM1 as Amber List (moderate evidence)
Mendeliome v1.52 RRM1 Seb Lunke Added comment: Comment on list classification: 3 families but only 2 Hom variants, not convinced they are definitely unrelated. 4th probed inconclusive.
Mendeliome v1.52 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.51 BUB1 Zornitza Stark Classified gene: BUB1 as Green List (high evidence)
Mendeliome v1.51 BUB1 Zornitza Stark Gene: bub1 has been classified as Green List (High Evidence).
Mendeliome v1.50 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Mendeliome v1.50 PAN2 Zornitza Stark Classified gene: PAN2 as Green List (high evidence)
Mendeliome v1.50 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Mendeliome v1.49 RRM1 Daniel Flanagan gene: RRM1 was added
gene: RRM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRM1 were set to 35617047
Phenotypes for gene: RRM1 were set to Multiple mitochondrial DNA deletion syndrome (MONDO:0016797)
Review for gene: RRM1 was set to GREEN
Added comment: Homozygous missense were identified in 4 four probands (p.Arg381Cys or p.Arg381His) from three families, who presented with ptosis and ophthalmoplegia, plus other manifestations and multiple mtDNA deletions in muscle. Heterozygous carriers were unaffected. An additional proband was heterozygous for a different RRM1 missense (p.Asn427Lys), another variant not identified.
Sources: Expert list
Mendeliome v1.49 LMOD2 Seb Lunke Gene: lmod2 has been classified as Green List (High Evidence).
Mendeliome v1.48 ATOH1 Zornitza Stark Gene: atoh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.48 LMOD2 Seb Lunke Classified gene: LMOD2 as Green List (high evidence)
Mendeliome v1.48 LMOD2 Seb Lunke Gene: lmod2 has been classified as Green List (High Evidence).
Mendeliome v1.47 PAN2 Naomi Baker gene: PAN2 was added
gene: PAN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to PMID:35304602; 29620724
Phenotypes for gene: PAN2 were set to Neurodevelopmental disorder, MONDO:0700092, PAN2-related
Review for gene: PAN2 was set to GREEN
Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck.

PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system.
Sources: Literature
Mendeliome v1.47 ATOH1 Zornitza Stark Phenotypes for gene: ATOH1 were changed from Pontocerebellar hypoplasia; developmental delay; hearing loss to Pontocerebellar hypoplasia MONDO:0020135, ATOH1-related
Mendeliome v1.46 ATOH1 Zornitza Stark Classified gene: ATOH1 as Amber List (moderate evidence)
Mendeliome v1.46 ATOH1 Zornitza Stark Gene: atoh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.46 PTPN13 Ain Roesley Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.46 PTPN13 Ain Roesley Classified gene: PTPN13 as Amber List (moderate evidence)
Mendeliome v1.46 PTPN13 Ain Roesley Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.45 PTPN13 Ain Roesley gene: PTPN13 was added
gene: PTPN13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN13 were set to 35643866
Phenotypes for gene: PTPN13 were set to bone marrow failure syndrome MONDO#0000159, PTPN13-related
Review for gene: PTPN13 was set to AMBER
gene: PTPN13 was marked as current diagnostic
Added comment: 2 families

Family A: 3 affecteds only 2 sequenced. Hom for a missense
3/3 Anaemia, 1x thrombocytopaenia, 1x severe neutropaenia, bone marrow with pure red cell aplasia
noted that the sibling who wasn't sequenced had normal bone marrow morphology

Family B: Chet for a missense and inframe del of 1 amino acid
Persistent hypogammaglobulinemia after transplant (at least 14 months after) with normal blood counts and Pre-B ALL with MLL rearrangement

In vitro studies of individual variants were LoF, including defective erythroid and megakaryocytic differentiation, consistent with anaemia and thrombocytopaenia reported in family A
Sources: Literature
Mendeliome v1.44 ATOH1 Chloe Stutterd gene: ATOH1 was added
gene: ATOH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATOH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATOH1 were set to 35518571
Phenotypes for gene: ATOH1 were set to Pontocerebellar hypoplasia; developmental delay; hearing loss
Penetrance for gene: ATOH1 were set to unknown
Review for gene: ATOH1 was set to AMBER
Added comment: Single report of novel homozygous missense variant in functional domain segregating with disease in two affected siblings with pontocerebellar hypoplasia, developmental delay and hearing loss. Similar phenotype previously reported in animal model with biallelic missense variant affecting same functional domain. Homology modelling predicts this missense variant affects binding capability of the bHLH domain to the DNA. Gene encodes a core transcription factor in developing cerebellum, brainstem, dorsal spinal cord and ear.
Sources: Literature
Mendeliome v1.44 BUB1 Paul De Fazio gene: BUB1 was added
gene: BUB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306
Phenotypes for gene: BUB1 were set to Intellectual disability and microcephaly
Review for gene: BUB1 was set to GREEN
gene: BUB1 was marked as current diagnostic
Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants:

P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable.
P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity.

BUB1 patient cells have impaired mitotic fidelity.

Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306)
Sources: Literature
Mendeliome v1.44 LMOD2 Melanie Marty gene: LMOD2 was added
gene: LMOD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LMOD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMOD2 were set to PMID: 31517052; PMID: 34888509; PMID: 35082396; PMID: 35188328; PMID: 26487682
Phenotypes for gene: LMOD2 were set to Dilated cardiomyopathy
Review for gene: LMOD2 was set to GREEN
Added comment: 4 unrelated families with early onset dilated cardiomyopathy, autosomal recessive inheritance, functional studies showing loss of protein and a mouse model reported.

PMID: 31517052 1 x neonate with DCM, homozygous nonsense variant identified.

PMID: 34888509 2 x neonatal deaths (from 1 family) related to dilated cardiomyopathy (DCM), compound heterozygous loss-of-function variants identified.

PMID:35082396 2 x siblings with DCM who died shortly after birth due to heart failure, homozygous canonical splice variant identified. Functional studies show loss of donor site and loss of protein.

PMID: 35188328 1 x child (9 months) with DCM, with homozygous frameshift variant. Functional studies showed absence of LMOD2 protein (western blot).

PMID: 26487682 Lmod2 null (knockout) mice present with short cardiac thin filaments and die at ~3 weeks due to dysfunctional, dilated hearts
Sources: Literature
Mendeliome v1.44 SEMA6B Zornitza Stark Phenotypes for gene: SEMA6B were changed from Progressive myoclonic epilepsy to Progressive myoclonic epilepsy; Intellectual disability, MONDO:0001071, SEMA6B related
Mendeliome v1.41 SRRM2 Zornitza Stark Classified gene: SRRM2 as Green List (high evidence)
Mendeliome v1.41 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Green List (High Evidence).
Mendeliome v1.40 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Mendeliome v1.40 GIMAP6 Elena Savva Classified gene: GIMAP6 as Green List (high evidence)
Mendeliome v1.40 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Mendeliome v1.38 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Mendeliome v1.36 HEATR3 Zornitza Stark Classified gene: HEATR3 as Green List (high evidence)
Mendeliome v1.36 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Mendeliome v1.35 GIMAP6 Elena Savva gene: GIMAP6 was added
gene: GIMAP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GIMAP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP6 were set to PMID: 35551368; 33328581
Phenotypes for gene: GIMAP6 were set to Autophagy, immune competence and inflammation
Review for gene: GIMAP6 was set to AMBER
Added comment: PMID: 35551368, PMID: 33328581
- K/O mice show autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)–containing lipids and die prematurely from microangiopathic glomerulosclerosis with immunodeficiency.
- 2 unrelated families (3 patients) w/ a homozygous missense (p.Gly153Val) and nonsense (p.Trp86*). All unaffected siblings were heterozygous.
Patient 1 (missense) presented with Coombs-positive hemolytic anemia, hepatosplenomegaly, Cranial MRI showed bilateral effusions, sulcal hyperintensity, and lateral parietal subcortical acute focal ischemic lesions.
Patient 2 (nonsense) presented with recurrent purulent otitis media and a chronic wet cough, persistent jaundice, recurrent chest and ear infections, lingular consolidation, mild bronchiectasis, bibasilar bronchial wall thickening, right peribronchial consolidation, right lower lobe bronchiectasis, bilateral axillary lymphadenopathy, and splenomegaly.
Patient 3 (nonsense) presented with suffered headaches, abdomen pain, mouth ulcers, and recurrent infections

- Functional studies show patient 1 (missense) with reduced protein expression on western blot, and patient 2/3 (nonsense) with no protein expression. T cells of Pt 1 were similar to mouse K/O model (elevated basal LC3-II, reduced autophagic flux).

gnomAD: 0 homozygous PTCs, but a very common canonical splice which is present in the non-canonical transcript
Sources: Literature
Mendeliome v1.34 HEATR3 Chern Lim gene: HEATR3 was added
gene: HEATR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to PMID: 35213692
Phenotypes for gene: HEATR3 were set to Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability
Review for gene: HEATR3 was set to GREEN
gene: HEATR3 was marked as current diagnostic
Added comment: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.
Sources: Literature
Mendeliome v1.34 TRIM47 Zornitza Stark Gene: trim47 has been classified as Red List (Low Evidence).
Mendeliome v1.34 TRIM47 Zornitza Stark gene: TRIM47 was added
gene: TRIM47 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM47 were set to 35511193
Phenotypes for gene: TRIM47 were set to Genetic cerebral small vessel disease MONDO:0018787
Review for gene: TRIM47 was set to RED
Added comment: GWAS data: Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. Observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology.
Sources: Literature
Mendeliome v1.33 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770 to Chorioretinal atrophy, progressive bifocal, MIM# 600790; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Mendeliome v1.28 SPTAN1 Zornitza Stark edited their review of gene: SPTAN1: Added comment: Leveille et al (2019) - 2 patients with HSP with biallelic missense SPTAN1 variants Previously described zebrafish, mouse, and rat animal models of SPTAN1 deficiency, all consistently showing axonal degeneration, fitting the pathological features of HSP in humans. Xie et al (2022) - 1 patient with complicated HSP and homozygous SPTAN1 mutation. Healthy parents and sister all carried the heterozygous mutation. Van de Vondel et al (2022) - 22 patients from 14 families with five novel heterozygous SPTAN1 variants. Presentations ranged from cerebellar ataxia, intellectual disability, epilepsy, and spastic paraplegia. A recurrent missense mutation (p.Arg19Trp) in 15 patients with spastic paraplegia. Through protein modeling they showed that mutated amino acids are located at crucial interlinking positions, interconnecting the three-helix bundle of a spectrin repeat.; Changed publications: 20493457, 22258530, 32811770, 35150594, 34526651, 31515523; Changed phenotypes: Developmental and epileptic encephalopathy 5, MIM# 613477, Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.22 AURKC Zornitza Stark Classified gene: AURKC as Green List (high evidence)
Mendeliome v1.22 AURKC Zornitza Stark Gene: aurkc has been classified as Green List (High Evidence).
Mendeliome v1.21 GJA5 Zornitza Stark Classified gene: GJA5 as Amber List (moderate evidence)
Mendeliome v1.21 GJA5 Zornitza Stark Gene: gja5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.18 TULP3 Zornitza Stark Phenotypes for gene: TULP3 were changed from progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045 to Hepatorenocardiac degenerative fibrosis, MIM# 619902
Mendeliome v1.17 TULP3 Zornitza Stark reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hepatorenocardiac degenerative fibrosis, MIM# 619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.16 IKBKG Zornitza Stark Phenotypes for gene: IKBKG were changed from Ectodermal dysplasia and immunodeficiency 1, MIM# 300291; Immunodeficiency 33 , MIM#300636; Incontinentia pigmenti, MIM# 308300 to Ectodermal dysplasia and immunodeficiency 1, MIM# 300291; Immunodeficiency 33 , MIM#300636; Incontinentia pigmenti, MIM# 308300; Autoinflammatory disease, systemic, X-linked, MIM# 301081
Mendeliome v1.15 IKBKG Zornitza Stark edited their review of gene: IKBKG: Added comment: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.; Changed phenotypes: Ectodermal dysplasia and immunodeficiency 1, MIM# 300291, Immunodeficiency 33 , MIM#300636, Incontinentia pigmenti, MIM# 308300, Autoinflammatory disease, systemic, X-linked, MIM# 301081
Mendeliome v1.15 MYO9A Zornitza Stark Classified gene: MYO9A as Amber List (moderate evidence)
Mendeliome v1.15 MYO9A Zornitza Stark Gene: myo9a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.13 FAT2 Elena Savva Classified gene: FAT2 as Green List (high evidence)
Mendeliome v1.13 FAT2 Elena Savva Gene: fat2 has been classified as Green List (High Evidence).
Mendeliome v1.12 GFRA1 Zornitza Stark Phenotypes for gene: GFRA1 were changed from Renal agenesis to Renal hypodysplasia/aplasia 4, MIM# 619887
Mendeliome v1.11 GFRA1 Zornitza Stark edited their review of gene: GFRA1: Changed phenotypes: Renal hypodysplasia/aplasia 4, MIM# 619887
Mendeliome v1.11 COPB2 Zornitza Stark Phenotypes for gene: COPB2 were changed from Microcephaly 19, primary, autosomal recessive, MIM# 617800; Osteoporosis and developmental delay to Microcephaly 19, primary, autosomal recessive, MIM# 617800; Osteoporosis, childhood- or juvenile-onset, with developmental delay, MIM# 619884
Mendeliome v1.10 ATP13A3 Zornitza Stark Phenotypes for gene: ATP13A3 were changed from Pulmonary arterial hypertension to Primary pulmonary hypertension 5, MIM#265400
Mendeliome v1.9 ATP13A3 Zornitza Stark edited their review of gene: ATP13A3: Changed phenotypes: Primary pulmonary hypertension 5, MIM#265400
Mendeliome v1.9 RBFOX2 Zornitza Stark Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.8 RBFOX2 Zornitza Stark Classified gene: RBFOX2 as Amber List (moderate evidence)
Mendeliome v1.8 RBFOX2 Zornitza Stark Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.7 PROSER1 Zornitza Stark Gene: proser1 has been classified as Red List (Low Evidence).
Mendeliome v1.7 PROSER1 Zornitza Stark gene: PROSER1 was added
gene: PROSER1 was added to Mendeliome. Sources: Expert Review
founder tags were added to gene: PROSER1.
Mode of inheritance for gene: PROSER1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PROSER1 were set to 35229282
Phenotypes for gene: PROSER1 were set to Syndromic disease MONDO:0002254, PROSER1-related
Review for gene: PROSER1 was set to RED
Added comment: 4 children from 3 related families with developmental delay, hypotonia, seizures, failure-to-thrive, strabismus, drooling, recurrent otitis media, hearing impairment, genitourinary malformations, and common facial features (arched eyebrows, prominent eyes, broad nasal bridge, low-hanging columella, open mouth, thick lower lip, protruding tongue, large low-set ears, and parietal bossing). WES revealed a homozygous frame-shift variant (p.Thr612Glnfs*22) in PROSER1. This encodes the proline and serine rich protein 1, part of the histone methyltransferases KMT2C/KMT2D complexes. PROSER1 stabilizes TET2, a member of the TET family of DNA demethylases which is involved in recruiting the enhancer-associated KMT2C/KMT2D complexes and mediating DNA demethylation, activating gene expression. Therefore, PROSER1 may play vital and potentially general roles in gene regulation. No functional assays and 3 related families, likely founder effect.
Sources: Expert Review
Mendeliome v1.6 SPATA22 Zornitza Stark Gene: spata22 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.6 SPATA22 Zornitza Stark Classified gene: SPATA22 as Amber List (moderate evidence)
Mendeliome v1.6 SPATA22 Zornitza Stark Gene: spata22 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5 SPATA22 Zornitza Stark gene: SPATA22 was added
gene: SPATA22 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SPATA22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA22 were set to 35285020
Phenotypes for gene: SPATA22 were set to Premature ovarian insufficiency and nonobstructive azoospermia; Genetic infertility MONDO:0017143
Review for gene: SPATA22 was set to AMBER
Added comment: 1 consanguineous family with two premature ovarian insufficiency (POI) and two nonobstructive azoospermia (NOA) patients. WES identified a homozygous variant in SPATA22 (c.400C>T:p.R134X). Histological analysis and spermatocyte spreading assay demonstrated that the spermatogenesis was arrested at a zygotene-like stage in the proband with NOA. 2nd patient found with idiopathic POI and compound heterozygous variants in SPATA22 (c.900+1G>A and c.31C>T:p.R11X).
Sources: Expert Review
Mendeliome v1.4 RDH11 Zornitza Stark Classified gene: RDH11 as Amber List (moderate evidence)
Mendeliome v1.4 RDH11 Zornitza Stark Gene: rdh11 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3 RDH11 Zornitza Stark edited their review of gene: RDH11: Added comment: 2nd case reported: 1 Chinese patient with retinitis pigmentosa, juvenile cataracts, intellectual disability, and myopathy. Trio-based WES and whole genomic CNV detection found compound heterozygous variants in RDH11 (p.Leu313Pro and c.75-3C>A) with biparental inheritance. Variant c.75-3C>A was confirmed to be a splice-site mutation by cDNA sequencing. It caused exon 2 skipping, resulting in a frameshift mutation and premature translation termination (p.Lys26Serfs*38). They found mislocalization of RDH11 protein in muscle cells of the patient by using immunofluorescence staining. Retinol dehydrogenase 11 (RDH11) is an 11-cis-retinol dehydrogenase that has a well-characterized, albeit auxiliary role in the retinoid cycle. Diseases caused by mutations in the RDH11 gene are very rare, and only one affected family with eye and intelligence involvement has been reported.; Changed rating: AMBER; Changed publications: 24916380, 15634683, 30731079, 18326732, 34988992
Mendeliome v1.0 Zornitza Stark promoted panel to version 1.0
Mendeliome v0.14798 GLRX3 Zornitza Stark Gene: glrx3 has been classified as Red List (Low Evidence).
Mendeliome v0.14797 DNM1L Zornitza Stark Gene: dnm1l has been classified as Green List (High Evidence).
Mendeliome v0.14797 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR); Optic atrophy 5 - MIM#610708 (AD)
Mendeliome v0.14795 DNASE1L3 Zornitza Stark Gene: dnase1l3 has been classified as Green List (High Evidence).
Mendeliome v0.14794 DNASE1 Zornitza Stark Gene: dnase1 has been classified as Red List (Low Evidence).
Mendeliome v0.14791 DNAJC6 Zornitza Stark Gene: dnajc6 has been classified as Green List (High Evidence).
Mendeliome v0.14788 DNASE1 Zornitza Stark Classified gene: DNASE1 as Red List (low evidence)
Mendeliome v0.14788 DNASE1 Zornitza Stark Gene: dnase1 has been classified as Red List (Low Evidence).
Mendeliome v0.14786 DNAJC5 Zornitza Stark Gene: dnajc5 has been classified as Green List (High Evidence).
Mendeliome v0.14786 DNAJC5 Zornitza Stark Phenotypes for gene: DNAJC5 were changed from to Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant - MIM#162350; ceroid lipofuscinosis, neuronal, 4 (Kufs type) - MONDO:0008083
Mendeliome v0.14784 DNAJC3 Zornitza Stark Gene: dnajc3 has been classified as Green List (High Evidence).
Mendeliome v0.14781 DNAJC21 Zornitza Stark Gene: dnajc21 has been classified as Green List (High Evidence).
Mendeliome v0.14779 DNM2 Zornitza Stark Gene: dnm2 has been classified as Green List (High Evidence).
Mendeliome v0.14775 DPY19L2 Zornitza Stark Gene: dpy19l2 has been classified as Green List (High Evidence).
Mendeliome v0.14774 AVPR2 Zornitza Stark Gene: avpr2 has been classified as Green List (High Evidence).
Mendeliome v0.14773 AVP Zornitza Stark Gene: avp has been classified as Green List (High Evidence).
Mendeliome v0.14773 AVP Zornitza Stark Phenotypes for gene: AVP were changed from to Diabetes insipidus, neurohypophyseal MIM#125700
Mendeliome v0.14772 DRAM2 Zornitza Stark Gene: dram2 has been classified as Green List (High Evidence).
Mendeliome v0.14767 DRD2 Zornitza Stark Gene: drd2 has been classified as Red List (Low Evidence).
Mendeliome v0.14767 ATP6V1E1 Zornitza Stark Gene: atp6v1e1 has been classified as Green List (High Evidence).
Mendeliome v0.14767 ATP6V1E1 Zornitza Stark Phenotypes for gene: ATP6V1E1 were changed from to Cutis laxa, autosomal recessive, type IIC MIM#617402
Mendeliome v0.14765 DRD2 Zornitza Stark Classified gene: DRD2 as Red List (low evidence)
Mendeliome v0.14765 DRD2 Zornitza Stark Gene: drd2 has been classified as Red List (Low Evidence).
Mendeliome v0.14764 DRD3 Zornitza Stark Gene: drd3 has been classified as Red List (Low Evidence).
Mendeliome v0.14761 DRD3 Zornitza Stark Classified gene: DRD3 as Red List (low evidence)
Mendeliome v0.14761 DRD3 Zornitza Stark Gene: drd3 has been classified as Red List (Low Evidence).
Mendeliome v0.14760 ATP2A1 Zornitza Stark Gene: atp2a1 has been classified as Green List (High Evidence).
Mendeliome v0.14758 DSC3 Zornitza Stark Gene: dsc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14758 DSC3 Zornitza Stark Phenotypes for gene: DSC3 were changed from to Hypotrichosis and recurrent skin vesicles MIM#613102
Mendeliome v0.14755 ADD1 Zornitza Stark Gene: add1 has been classified as Green List (High Evidence).
Mendeliome v0.14755 ADD1 Zornitza Stark Phenotypes for gene: ADD1 were changed from Intellectual disability, corpus callosum dysgenesis, and ventriculomegaly; no OMIM # to Neurodevelopmental disorder MONDO:0700092, ADD1-related
Mendeliome v0.14754 DSC3 Zornitza Stark Classified gene: DSC3 as Amber List (moderate evidence)
Mendeliome v0.14754 DSC3 Zornitza Stark Gene: dsc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14753 DSCAM Zornitza Stark Gene: dscam has been classified as Green List (High Evidence).
Mendeliome v0.14751 DSCAM Zornitza Stark Classified gene: DSCAM as Green List (high evidence)
Mendeliome v0.14751 DSCAM Zornitza Stark Gene: dscam has been classified as Green List (High Evidence).
Mendeliome v0.14749 DSCAM Zornitza Stark Classified gene: DSCAM as Amber List (moderate evidence)
Mendeliome v0.14749 DSCAM Zornitza Stark Gene: dscam has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14748 DSE Zornitza Stark Gene: dse has been classified as Green List (High Evidence).
Mendeliome v0.14745 DSG4 Zornitza Stark Gene: dsg4 has been classified as Green List (High Evidence).
Mendeliome v0.14745 DSG4 Zornitza Stark Phenotypes for gene: DSG4 were changed from to Hypotrichosis 6 - MIM#607903
Mendeliome v0.14742 DSPP Zornitza Stark Gene: dspp has been classified as Green List (High Evidence).
Mendeliome v0.14742 DSPP Zornitza Stark Phenotypes for gene: DSPP were changed from to Deafness, autosomal dominant 39, with dentinogenesis - MIM#605594; Dentin dysplasia, type II - MIM#125420; Dentinogenesis imperfecta, Shields type II - MIM#125490; Dentinogenesis imperfecta, Shields type III - MIM#125500
Mendeliome v0.14740 DUOX2 Zornitza Stark Gene: duox2 has been classified as Green List (High Evidence).
Mendeliome v0.14740 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from to Thyroid dyshormonogenesis 6 - MIM#607200
Mendeliome v0.14738 GDNF Elena Savva Gene: gdnf has been classified as Red List (Low Evidence).
Mendeliome v0.14738 DUOXA2 Zornitza Stark Gene: duoxa2 has been classified as Green List (High Evidence).
Mendeliome v0.14738 DUOXA2 Zornitza Stark Phenotypes for gene: DUOXA2 were changed from to Thyroid dyshormonogenesis 5 - MIM#274900
Mendeliome v0.14736 ENPP1 Zornitza Stark Gene: enpp1 has been classified as Green List (High Evidence).
Mendeliome v0.14736 EPOR Zornitza Stark Gene: epor has been classified as Green List (High Evidence).
Mendeliome v0.14736 EPRS Zornitza Stark Gene: eprs has been classified as Green List (High Evidence).
Mendeliome v0.14736 EPS8 Zornitza Stark Gene: eps8 has been classified as Green List (High Evidence).
Mendeliome v0.14736 EPS8 Zornitza Stark Phenotypes for gene: EPS8 were changed from to Autosomal recessive nonsyndromic hearing loss 102 MONDO:0014428
Mendeliome v0.14733 ETFB Zornitza Stark Gene: etfb has been classified as Green List (High Evidence).
Mendeliome v0.14732 EXT1 Zornitza Stark Gene: ext1 has been classified as Green List (High Evidence).
Mendeliome v0.14731 EYA4 Zornitza Stark Gene: eya4 has been classified as Green List (High Evidence).
Mendeliome v0.14731 EYS Zornitza Stark Gene: eys has been classified as Green List (High Evidence).
Mendeliome v0.14728 FXR1 Zornitza Stark Gene: fxr1 has been classified as Green List (High Evidence).
Mendeliome v0.14728 ETV2 Ain Roesley Gene: etv2 has been classified as Red List (Low Evidence).
Mendeliome v0.14727 GABRB2 Zornitza Stark Gene: gabrb2 has been classified as Green List (High Evidence).
Mendeliome v0.14726 GALNT2 Zornitza Stark Gene: galnt2 has been classified as Green List (High Evidence).
Mendeliome v0.14725 GALNT3 Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence).
Mendeliome v0.14725 GALNT3 Zornitza Stark Phenotypes for gene: GALNT3 were changed from to Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900
Mendeliome v0.14722 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Mendeliome v0.14719 GAMT Zornitza Stark Gene: gamt has been classified as Green List (High Evidence).
Mendeliome v0.14716 GAN Zornitza Stark Gene: gan has been classified as Green List (High Evidence).
Mendeliome v0.14713 GBA2 Zornitza Stark Gene: gba2 has been classified as Green List (High Evidence).
Mendeliome v0.14713 GBA2 Zornitza Stark Phenotypes for gene: GBA2 were changed from to Spastic paraplegia 46, autosomal recessive, MIM# 614409; MONDO:0013737
Mendeliome v0.14710 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Mendeliome v0.14707 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Mendeliome v0.14707 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230
Mendeliome v0.14704 GCK Zornitza Stark Gene: gck has been classified as Green List (High Evidence).
Mendeliome v0.14701 GCNT2 Zornitza Stark Gene: gcnt2 has been classified as Green List (High Evidence).
Mendeliome v0.14697 GDAP1 Zornitza Stark Gene: gdap1 has been classified as Green List (High Evidence).
Mendeliome v0.14697 GDAP1 Zornitza Stark Phenotypes for gene: GDAP1 were changed from to Charcot-Marie-Tooth disease, axonal, type 2K 607831, MIM# Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM# 607706; Charcot-Marie-Tooth disease, recessive intermediate, A, MIM# 608340; Charcot-Marie-Tooth disease, type 4A, MIM# 214400
Mendeliome v0.14694 GATAD1 Elena Savva Gene: gatad1 has been classified as Red List (Low Evidence).
Mendeliome v0.14693 FBXW4 Elena Savva Gene: fbxw4 has been classified as Red List (Low Evidence).
Mendeliome v0.14692 AURKC Elena Savva Gene: aurkc has been classified as Red List (Low Evidence).
Mendeliome v0.14691 ATPAF2 Elena Savva Gene: atpaf2 has been classified as Red List (Low Evidence).
Mendeliome v0.14691 ATP2C2 Elena Savva Gene: atp2c2 has been classified as Red List (Low Evidence).
Mendeliome v0.14691 AHSG Elena Savva Gene: ahsg has been classified as Red List (Low Evidence).
Mendeliome v0.14689 GDF2 Zornitza Stark Gene: gdf2 has been classified as Green List (High Evidence).
Mendeliome v0.14689 GDF2 Zornitza Stark Phenotypes for gene: GDF2 were changed from to Telangiectasia, hereditary hemorrhagic, type 5 OMIM # 615506; pulmonary arteriovenous malformations
Mendeliome v0.14686 GDF9 Zornitza Stark Gene: gdf9 has been classified as Green List (High Evidence).
Mendeliome v0.14683 GEMIN4 Zornitza Stark Gene: gemin4 has been classified as Green List (High Evidence).
Mendeliome v0.14680 GFM2 Zornitza Stark Gene: gfm2 has been classified as Green List (High Evidence).
Mendeliome v0.14677 GIF Zornitza Stark Gene: gif has been classified as Green List (High Evidence).
Mendeliome v0.14677 GIF Zornitza Stark Phenotypes for gene: GIF were changed from to Intrinsic factor deficiency MIM#261000; Disorders of cobalamin absorption, transport and metabolism
Mendeliome v0.14672 SLC26A1 Elena Savva Gene: slc26a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14672 TIA1 Elena Savva Phenotypes for gene: TIA1 were changed from Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454) to Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454)
Mendeliome v0.14670 PRKAG3 Elena Savva Gene: prkag3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14670 GINS1 Zornitza Stark Gene: gins1 has been classified as Green List (High Evidence).
Mendeliome v0.14667 U2AF2 Elena Savva Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14667 TDP1 Elena Savva Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14667 TIA1 Elena Savva Phenotypes for gene: TIA1 were changed from to Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454)
Mendeliome v0.14666 TIA1 Elena Savva Gene: tia1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 PLD3 Elena Savva Gene: pld3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 RBM7 Elena Savva Gene: rbm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 MFAP5 Elena Savva Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 MMGT1 Elena Savva Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 FRA12A Elena Savva Str: fra12a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 GIGYF2 Elena Savva Gene: gigyf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14665 MEPE Elena Savva Gene: mepe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14665 LRIF1 Elena Savva Gene: lrif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14663 DMGDH Elena Savva Gene: dmgdh has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14662 DCAF8 Elena Savva Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14662 CCT5 Elena Savva Gene: cct5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14662 ATG5 Elena Savva Gene: atg5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14662 LYZ Abhijit Kulkarni reviewed gene: LYZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 1808634 8464497 15745733; Phenotypes: Amyloidosis, renal (MIM: 105200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14662 USP8 Elena Savva Gene: usp8 has been classified as Green List (High Evidence).
Mendeliome v0.14662 LRP5 Krithika Murali reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Exudative vitreoretinopathy 4 - MIM#601813 (AD, AR), Hyperostosis, endosteal - MIM#144750 (AD), Osteopetrosis, autosomal dominant 1 - MIM#607634(AD), Osteoporosis-pseudoglioma syndrome - MIM#259770 (AR), Osteosclerosis - #144750 (AD), Polycystic liver disease 4 with or without kidney cysts - MIM#617875 (AD), van Buchem disease, type 2 - MIM#607636; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14662 MSX1 Elena Savva Phenotypes for gene: MSX1 were changed from Witkop syndrome (Ectodermal Dysplasia) (MIM: 189500),Cleft Lip+/- Cleft Palate (Rofacial Cleft- MIM :608874), Oligodontia to Witkop syndrome (Ectodermal Dysplasia) (MIM: 189500),Cleft Lip+/- Cleft Palate (Rofacial Cleft- MIM :608874), Oligodontia
Mendeliome v0.14660 LRP6 Krithika Murali reviewed gene: LRP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26387593; Phenotypes: Tooth agenesis, selective, 7 - MIM#616724; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14660 MSX1 Elena Savva Phenotypes for gene: MSX1 were changed from to Witkop syndrome (Ectodermal Dysplasia) (MIM: 189500),Cleft Lip+/- Cleft Palate (Rofacial Cleft- MIM :608874), Oligodontia
Mendeliome v0.14659 MSX1 Elena Savva Gene: msx1 has been classified as Green List (High Evidence).
Mendeliome v0.14658 LYZ Krithika Murali reviewed gene: LYZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 1808634, 8464497, 15745733,; Phenotypes: Amyloidosis, renal - MIM#105200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14657 GJA1 Zornitza Stark Gene: gja1 has been classified as Green List (High Evidence).
Mendeliome v0.14657 GJA1 Zornitza Stark Phenotypes for gene: GJA1 were changed from to Oculodentodigital dysplasia, autosomal recessive, MIM# 257850; Oculodentodigital dysplasia, MIM# 164200
Mendeliome v0.14654 GJA5 Zornitza Stark Gene: gja5 has been classified as Green List (High Evidence).
Mendeliome v0.14651 LRP2 Chirag Patel commented on gene: LRP2: Donnai-Barrow syndrome (DBS) was first described as a distinct disorder characterized by diaphragmatic hernia, exomphalos, absent corpus callosum, myopia, agenesis of the corpus callosum and proteinuria, and sensorineural deafness.

Kantarci et al. (2007) identified biallelic LRP2 mutations in 6 families with Donnai-Barrow syndrome and one family with facio-oculo-acoustico-renal syndrome.
Mendeliome v0.14651 LINS1 Chirag Patel reviewed gene: LINS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32802957, 34450347, 32499722, 31922598; Phenotypes: Intellectual developmental disorder, autosomal recessive 27, MIM# 614340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14651 ADD1 Chirag Patel Classified gene: ADD1 as Green List (high evidence)
Mendeliome v0.14651 ADD1 Chirag Patel Gene: add1 has been classified as Green List (High Evidence).
Mendeliome v0.14650 ADD1 Chirag Patel gene: ADD1 was added
gene: ADD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADD1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ADD1 were set to PMID: 34906466
Phenotypes for gene: ADD1 were set to Intellectual disability, corpus callosum dysgenesis, and ventriculomegaly; no OMIM #
Review for gene: ADD1 was set to GREEN
Added comment: 4 unrelated individuals affected by ID and/or complete or partial agenesis of corpus callosum, and enlarged lateral ventricles. WES found loss-of-function variants - 1 recessive missense variant and 3 de novo variants. The recessive variant is associated with ACC and enlarged lateral ventricles, and the de novo variants were associated with complete or partial agenesis of corpus callosum, mild ID and attention deficit. Human variants impair ADD1 protein expression and/or dimerization with ADD2. Add1 knockout mice recapitulate corpus callosum dysgenesis and ventriculomegaly phenotypes. Three adducin genes (ADD1, ADD2, and ADD3) encode cytoskeleton proteins that are critical for osmotic rigidity and cell shape. ADD1, ADD2, and ADD3 form heterodimers (ADD1/ADD2, ADD1/ADD3), which further form heterotetramers. Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown
Sources: Literature
Mendeliome v0.14649 AVP Chirag Patel reviewed gene: AVP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 6526016, 1840604, 8554046; Phenotypes: Diabetes insipidus, neurohypophyseal MIM#125700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14649 AURKC Chirag Patel Classified gene: AURKC as Red List (low evidence)
Mendeliome v0.14649 AURKC Chirag Patel Gene: aurkc has been classified as Red List (Low Evidence).
Mendeliome v0.14649 AURKC Chirag Patel Classified gene: AURKC as Red List (low evidence)
Mendeliome v0.14649 AURKC Chirag Patel Gene: aurkc has been classified as Red List (Low Evidence).
Mendeliome v0.14649 AURKC Chirag Patel Classified gene: AURKC as Red List (low evidence)
Mendeliome v0.14649 AURKC Chirag Patel Gene: aurkc has been classified as Red List (Low Evidence).
Mendeliome v0.14648 ATPAF2 Chirag Patel Classified gene: ATPAF2 as Red List (low evidence)
Mendeliome v0.14648 ATPAF2 Chirag Patel Gene: atpaf2 has been classified as Red List (Low Evidence).
Mendeliome v0.14648 ATPAF2 Chirag Patel Classified gene: ATPAF2 as Red List (low evidence)
Mendeliome v0.14648 ATPAF2 Chirag Patel Gene: atpaf2 has been classified as Red List (Low Evidence).
Mendeliome v0.14647 ATP6V1E1 Chirag Patel reviewed gene: ATP6V1E1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28065471, 27023906; Phenotypes: Cutis laxa, autosomal recessive, type IIC MIM#617402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14647 GJA5 Chirag Patel commented on gene: GJA5: Gollob et al. (2006) presented evidence that tissue-specific mutations in the GJA5 gene may predispose the atria to fibrillation. They identified a heterozygous missense mutation in blood and cardiac tissue in patient with AF. They also found 3 heterozygous missense mutations in cardiac tissue only in 3 other patients, indicating a somatic source of the genetic defects

Yang et al. (2010) identified a heterozygous nonsense mutationin a 64-year-old female patient who was diagnosed with paroxysmal AF at 32 years of age. The mutation was detected in 6 additional affected family members, but was not found in 6 unaffected family members or in 200 ethnically matched controls.

Yang et al. (2010) identified 3 heterozygous missense mutations in 3 probands with AF. The mutations segregated with disease in all 3 families and were not found in 200 ethnically matched controls.

Sun et al. (2013) identified a heterozygous missense mutation in a 42-year-old woman who had been diagnosed with AF at age 40 years. The mutation was also detected in her father, who had been diagnosed with lone AF at 41 years of age, but it was not found in unaffected family members, in 200 controls, or in the dbSNP database. Functional analysis demonstrated that the I75F mutant is unable to form functional gap junction channels and also impairs coupling when expressed with wildtype CX40 or CX43.
Mendeliome v0.14647 GJB2 Zornitza Stark Gene: gjb2 has been classified as Green List (High Evidence).
Mendeliome v0.14647 GJB2 Zornitza Stark Phenotypes for gene: GJB2 were changed from to Bart-Pumphrey syndrome, MIM#149200; Deafness, autosomal dominant 3A, MIM#601544; Deafness, autosomal recessive 1A, MIM#220290; Hystrix-like ichthyosis with deafness, MIM#602540; Keratitis-ichthyosis-deafness syndrome, MIM#148210; Keratoderma, palmoplantar, with deafness, MIM#148350; Vohwinkel syndrome, MIM# 124500
Mendeliome v0.14644 GJB3 Zornitza Stark Gene: gjb3 has been classified as Green List (High Evidence).
Mendeliome v0.14644 GJB3 Zornitza Stark Phenotypes for gene: GJB3 were changed from to Erythrokeratodermia variabilis et progressiva 1, MIM# 133200
Mendeliome v0.14642 GJB2 Chirag Patel reviewed gene: GJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11179004, 9529365, 14985372, 19941053, 11354642; Phenotypes: Bart-Pumphrey syndrome, MIM#149200, Deafness, autosomal dominant 3A, MIM#601544, Deafness, autosomal recessive 1A, MIM#220290, Hystrix-like ichthyosis with deafness, MIM#602540, Keratitis-ichthyosis-deafness syndrome, MIM#148210, Keratoderma, palmoplantar, with deafness, MIM#148350, Vohwinkel syndrome, MIM# 124500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14640 GJB3 Zornitza Stark reviewed gene: GJB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843209, 10594760, 10798362, 12019212; Phenotypes: Erythrokeratodermia variabilis et progressiva 1, MIM# 133200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14640 GJB3 Chirag Patel reviewed gene: GJB3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9843209, 10798362, 10594760, 17446259, 9843210; Phenotypes: Erythrokeratodermia variabilis et progressiva 1, OMIM #133200, Deafness, autosomal dominant 2B, OMIM # 612644; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14640 GJB4 Zornitza Stark Gene: gjb4 has been classified as Green List (High Evidence).
Mendeliome v0.14640 GJB4 Zornitza Stark Phenotypes for gene: GJB4 were changed from to Erythrokeratodermia variabilis et progressiva 2, MIM# 617524
Mendeliome v0.14637 GJB4 Zornitza Stark reviewed gene: GJB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11017804, 12648223, 19291775; Phenotypes: Erythrokeratodermia variabilis et progressiva 2, MIM# 617524; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14637 GJB6 Zornitza Stark Gene: gjb6 has been classified as Green List (High Evidence).
Mendeliome v0.14637 GJB6 Zornitza Stark Phenotypes for gene: GJB6 were changed from to Deafness, autosomal dominant 3B, MIM# 612643; Deafness, autosomal recessive 1B, MIM# 612645; Ectodermal dysplasia 2, Clouston type, MIM# 129500
Mendeliome v0.14634 GJB6 Zornitza Stark reviewed gene: GJB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 11017065, 23219093, 11874494, 18717672, 27137747, 25808784, 19416251, 26620415, 17227867; Phenotypes: Deafness, autosomal dominant 3B, MIM# 612643, Deafness, autosomal recessive 1B, MIM# 612645, Ectodermal dysplasia 2, Clouston type, MIM# 129500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14634 GK Zornitza Stark Gene: gk has been classified as Green List (High Evidence).
Mendeliome v0.14631 GLCCI1 Zornitza Stark Gene: glcci1 has been classified as Red List (Low Evidence).
Mendeliome v0.14629 GLCCI1 Zornitza Stark Classified gene: GLCCI1 as Red List (low evidence)
Mendeliome v0.14629 GLCCI1 Zornitza Stark Gene: glcci1 has been classified as Red List (Low Evidence).
Mendeliome v0.14628 GLE1 Zornitza Stark Gene: gle1 has been classified as Green List (High Evidence).
Mendeliome v0.14625 GLIS3 Zornitza Stark Gene: glis3 has been classified as Green List (High Evidence).
Mendeliome v0.14622 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Mendeliome v0.14619 GLYCTK Zornitza Stark Gene: glyctk has been classified as Green List (High Evidence).
Mendeliome v0.14616 GMPPA Zornitza Stark Gene: gmppa has been classified as Green List (High Evidence).
Mendeliome v0.14616 GMPPA Zornitza Stark Phenotypes for gene: GMPPA were changed from to Alacrima, achalasia, and mental retardation syndrome, MIM# 615510
Mendeliome v0.14613 GMPPA Zornitza Stark reviewed gene: GMPPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 24035193, 28574218; Phenotypes: Alacrima, achalasia, and mental retardation syndrome, MIM# 615510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14613 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Mendeliome v0.14611 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Mendeliome v0.14611 GNAS Zornitza Stark Phenotypes for gene: GNAS were changed from to 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 v0.14609 GNAS Zornitza Stark reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 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); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14609 GNAT1 Zornitza Stark Gene: gnat1 has been classified as Green List (High Evidence).
Mendeliome v0.14606 GNB3 Zornitza Stark Gene: gnb3 has been classified as Green List (High Evidence).
Mendeliome v0.14603 GNMT Zornitza Stark Gene: gnmt has been classified as Green List (High Evidence).
Mendeliome v0.14600 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Green List (High Evidence).
Mendeliome v0.14600 GOSR2 Zornitza Stark Phenotypes for gene: GOSR2 were changed from to Epilepsy, progressive myoclonic 6 , MIM#614018
Mendeliome v0.14597 GOSR2 Zornitza Stark reviewed gene: GOSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21549339, 24458321, 30363482; Phenotypes: Epilepsy, progressive myoclonic 6 , MIM#614018; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14597 GOT1 Zornitza Stark Gene: got1 has been classified as Red List (Low Evidence).
Mendeliome v0.14596 GOT1 Zornitza Stark Classified gene: GOT1 as Red List (low evidence)
Mendeliome v0.14596 GOT1 Zornitza Stark Gene: got1 has been classified as Red List (Low Evidence).
Mendeliome v0.14595 GPC4 Zornitza Stark Gene: gpc4 has been classified as Green List (High Evidence).
Mendeliome v0.14592 GPNMB Krithika Murali reviewed gene: GPNMB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31226264, 29336782, 31260093, 34551863, 33687658; Phenotypes: Amyloidosis, primary localized cutaneous, 3 - MIM#617920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14592 GDF2 Chirag Patel reviewed gene: GDF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23972370, 27081547, 32573726, 32992168, 34611981, 33834622, 32669404, 26056270, 23972370; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5 OMIM # 615506, pulmonary arteriovenous malformations; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14592 GJA1 Chirag Patel reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19338053; Phenotypes: Oculodentodigital dysplasia, autosomal recessive, MIM# 257850, Oculodentodigital dysplasia, MIM# 164200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14592 GDNF Chirag Patel Classified gene: GDNF as Red List (low evidence)
Mendeliome v0.14592 GDNF Chirag Patel Gene: gdnf has been classified as Red List (Low Evidence).
Mendeliome v0.14590 GIGYF2 Chirag Patel Classified gene: GIGYF2 as Amber List (moderate evidence)
Mendeliome v0.14590 GIGYF2 Chirag Patel Gene: gigyf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14589 HEY2 Zornitza Stark Gene: hey2 has been classified as Red List (Low Evidence).
Mendeliome v0.14588 GCH1 Chirag Patel reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 7874165, 11113234, 15753436, 9667588, 10987649, 32170445, 32278297, 32746945, 30314816; Phenotypes: Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910, Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14588 IL18BP Zornitza Stark Gene: il18bp has been classified as Red List (Low Evidence).
Mendeliome v0.14588 ITPKB Zornitza Stark Gene: itpkb has been classified as Red List (Low Evidence).
Mendeliome v0.14587 MUC7 Zornitza Stark Gene: muc7 has been classified as Red List (Low Evidence).
Mendeliome v0.14585 MYF6 Zornitza Stark Gene: myf6 has been classified as Red List (Low Evidence).
Mendeliome v0.14582 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14581 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Mendeliome v0.14581 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14580 POU5F1 Zornitza Stark Gene: pou5f1 has been classified as Red List (Low Evidence).
Mendeliome v0.14580 GBA2 Chirag Patel reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23332916, 23332917, 29524657; Phenotypes: Spastic paraplegia 46, autosomal recessive, MIM# 614409, MONDO:0013737; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14580 GATAD1 Chirag Patel Classified gene: GATAD1 as Red List (low evidence)
Mendeliome v0.14580 GATAD1 Chirag Patel Gene: gatad1 has been classified as Red List (Low Evidence).
Mendeliome v0.14579 SGK3 Zornitza Stark Gene: sgk3 has been classified as Red List (Low Evidence).
Mendeliome v0.14579 GALNT3 Chirag Patel reviewed gene: GALNT3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15133511, 20358599, 32125652; Phenotypes: Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14579 GPD1 Zornitza Stark Gene: gpd1 has been classified as Green List (High Evidence).
Mendeliome v0.14579 GPD1 Zornitza Stark Phenotypes for gene: GPD1 were changed from to Hypertriglyceridemia, transient infantile MIM#614480; glycerol-3-phosphate dehydrogenase deficiency
Mendeliome v0.14576 GPD1 Zornitza Stark reviewed gene: GPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22226083, 24549054, 35365473, 34484308, 33447932; Phenotypes: Hypertriglyceridaemia, transient infantile, MIM# 614480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14576 GPHN Zornitza Stark Gene: gphn has been classified as Green List (High Evidence).
Mendeliome v0.14575 GPNMB Zornitza Stark Gene: gpnmb has been classified as Green List (High Evidence).
Mendeliome v0.14575 GPNMB Zornitza Stark Phenotypes for gene: GPNMB were changed from to Amyloidosis, primary localized cutaneous, 3, MIM# 617920
Mendeliome v0.14572 GPNMB Zornitza Stark reviewed gene: GPNMB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29336782; Phenotypes: Amyloidosis, primary localized cutaneous, 3, MIM# 617920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14572 GREM1 Zornitza Stark Gene: grem1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14572 GREM1 Zornitza Stark Phenotypes for gene: GREM1 were changed from to Genetic intestinal polyposis MONDO:0018188
Mendeliome v0.14569 GREM1 Zornitza Stark Classified gene: GREM1 as Amber List (moderate evidence)
Mendeliome v0.14569 GREM1 Zornitza Stark Gene: grem1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14568 MRAP Zornitza Stark Gene: mrap has been classified as Green List (High Evidence).
Mendeliome v0.14565 MPZL2 Zornitza Stark Gene: mpzl2 has been classified as Green List (High Evidence).
Mendeliome v0.14565 MPZL2 Zornitza Stark Phenotypes for gene: MPZL2 were changed from to Deafness, autosomal recessive 111, MIM#618145
Mendeliome v0.14562 MPZL2 Zornitza Stark reviewed gene: MPZL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29982980, 29961571; Phenotypes: Deafness, autosomal recessive 111, MIM#618145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14562 MPZ Zornitza Stark Gene: mpz has been classified as Green List (High Evidence).
Mendeliome v0.14559 MPV17 Zornitza Stark Gene: mpv17 has been classified as Green List (High Evidence).
Mendeliome v0.14556 MPO Zornitza Stark Gene: mpo has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14554 MPO Zornitza Stark Classified gene: MPO as Amber List (moderate evidence)
Mendeliome v0.14554 MPO Zornitza Stark Gene: mpo has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14553 MPC1 Zornitza Stark Gene: mpc1 has been classified as Green List (High Evidence).
Mendeliome v0.14550 MOG Zornitza Stark Gene: mog has been classified as Red List (Low Evidence).
Mendeliome v0.14547 MOG Zornitza Stark Classified gene: MOG as Red List (low evidence)
Mendeliome v0.14547 MOG Zornitza Stark Gene: mog has been classified as Red List (Low Evidence).
Mendeliome v0.14546 MOCS3 Zornitza Stark Gene: mocs3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14543 MOCS3 Zornitza Stark Classified gene: MOCS3 as Amber List (moderate evidence)
Mendeliome v0.14543 MOCS3 Zornitza Stark Gene: mocs3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14542 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Green List (High Evidence).
Mendeliome v0.14541 MNX1 Zornitza Stark Gene: mnx1 has been classified as Green List (High Evidence).
Mendeliome v0.14538 MMP2 Zornitza Stark Gene: mmp2 has been classified as Green List (High Evidence).
Mendeliome v0.14538 MMP2 Zornitza Stark Phenotypes for gene: MMP2 were changed from to Multicentric osteolysis, nodulosis, and arthropathy, MIM# 259600
Mendeliome v0.14535 MMP2 Zornitza Stark reviewed gene: MMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11431697, 15691365, 17059372, 17400654; Phenotypes: Multicentric osteolysis, nodulosis, and arthropathy, MIM# 259600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14533 ATP6V1A Elena Savva Gene: atp6v1a has been classified as Green List (High Evidence).
Mendeliome v0.14533 ATP6V1A Elena Savva Phenotypes for gene: ATP6V1A were changed from to Cutis laxa, autosomal recessive, type IID MIM#617403; Developmental and epileptic encephalopathy 93 MIM#618012
Mendeliome v0.14532 ATP6V1A Elena Savva reviewed gene: ATP6V1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29668857, 28065471, 33320377; Phenotypes: Cutis laxa, autosomal recessive, type IID MIM#617403, Developmental and epileptic encephalopathy 93 MIM#618012; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14531 ATP6AP2 Elena Savva Gene: atp6ap2 has been classified as Green List (High Evidence).
Mendeliome v0.14530 MMADHC Zornitza Stark Gene: mmadhc has been classified as Green List (High Evidence).
Mendeliome v0.14527 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Mendeliome v0.14524 MMAB Zornitza Stark Gene: mmab has been classified as Green List (High Evidence).
Mendeliome v0.14524 MMAB Zornitza Stark Phenotypes for gene: MMAB were changed from to Methylmalonic aciduria, vitamin B12-responsive, cblB type, MIM# 251110
Mendeliome v0.14522 MMAB Zornitza Stark reviewed gene: MMAB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblB type, MIM# 251110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14522 MMAA Zornitza Stark Gene: mmaa has been classified as Green List (High Evidence).
Mendeliome v0.14522 MMAA Zornitza Stark Phenotypes for gene: MMAA were changed from to Methylmalonic aciduria, vitamin B12-responsive, cblA type, MIM# 251100
Mendeliome v0.14520 MMAA Zornitza Stark reviewed gene: MMAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblA type, MIM# 251100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14520 MLPH Zornitza Stark Gene: mlph has been classified as Green List (High Evidence).
Mendeliome v0.14517 MITF Zornitza Stark Gene: mitf has been classified as Green List (High Evidence).
Mendeliome v0.14514 MIR936 Zornitza Stark Gene: mir936 has been classified as Red List (Low Evidence).
Mendeliome v0.14514 MIR936 Zornitza Stark Classified gene: MIR936 as Red List (low evidence)
Mendeliome v0.14514 MIR936 Zornitza Stark Gene: mir936 has been classified as Red List (Low Evidence).
Mendeliome v0.14513 MIR184 Zornitza Stark Gene: mir184 has been classified as Green List (High Evidence).
Mendeliome v0.14510 MIR183 Zornitza Stark Gene: mir183 has been classified as Red List (Low Evidence).
Mendeliome v0.14510 MIR183 Zornitza Stark Classified gene: MIR183 as Red List (low evidence)
Mendeliome v0.14510 MIR183 Zornitza Stark Gene: mir183 has been classified as Red List (Low Evidence).
Mendeliome v0.14506 ATP2C1 Elena Savva Gene: atp2c1 has been classified as Green List (High Evidence).
Mendeliome v0.14505 ATP6V0A1 Elena Savva Gene: atp6v0a1 has been classified as Green List (High Evidence).
Mendeliome v0.14505 MIR182 Zornitza Stark Gene: mir182 has been classified as Red List (Low Evidence).
Mendeliome v0.14505 MIR182 Zornitza Stark Classified gene: MIR182 as Red List (low evidence)
Mendeliome v0.14505 MIR182 Zornitza Stark Gene: mir182 has been classified as Red List (Low Evidence).
Mendeliome v0.14504 MIP Zornitza Stark Gene: mip has been classified as Green List (High Evidence).
Mendeliome v0.14501 MIF Zornitza Stark Gene: mif has been classified as Red List (Low Evidence).
Mendeliome v0.14499 MIF Zornitza Stark Classified gene: MIF as Red List (low evidence)
Mendeliome v0.14499 MIF Zornitza Stark Gene: mif has been classified as Red List (Low Evidence).
Mendeliome v0.14498 MGME1 Zornitza Stark Gene: mgme1 has been classified as Green List (High Evidence).
Mendeliome v0.14495 MFN2 Zornitza Stark Gene: mfn2 has been classified as Green List (High Evidence).
Mendeliome v0.14494 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Mendeliome v0.14494 MFF Zornitza Stark Phenotypes for gene: MFF were changed from to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086
Mendeliome v0.14491 MFF Zornitza Stark reviewed gene: MFF: Rating: GREEN; Mode of pathogenicity: None; Publications: 22499341, 26783368, 32181496]; Phenotypes: Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14491 METTL23 Zornitza Stark Gene: mettl23 has been classified as Green List (High Evidence).
Mendeliome v0.14491 METTL23 Zornitza Stark Phenotypes for gene: METTL23 were changed from to Intellectual developmental disorder, autosomal recessive 44, MIM# 615942
Mendeliome v0.14488 METTL23 Zornitza Stark reviewed gene: METTL23: Rating: GREEN; Mode of pathogenicity: None; Publications: 24501276, 24626631; Phenotypes: Intellectual developmental disorder, autosomal recessive 44, MIM# 615942; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14488 MET Zornitza Stark Gene: met has been classified as Green List (High Evidence).
Mendeliome v0.14486 ATG16L1 Elena Savva Gene: atg16l1 has been classified as Red List (Low Evidence).
Mendeliome v0.14486 MERTK Zornitza Stark Gene: mertk has been classified as Green List (High Evidence).
Mendeliome v0.14483 MEIS1 Zornitza Stark Gene: meis1 has been classified as Red List (Low Evidence).
Mendeliome v0.14483 MEIS1 Zornitza Stark Classified gene: MEIS1 as Red List (low evidence)
Mendeliome v0.14483 MEIS1 Zornitza Stark Gene: meis1 has been classified as Red List (Low Evidence).
Mendeliome v0.14481 ATP2A2 Elena Savva Gene: atp2a2 has been classified as Green List (High Evidence).
Mendeliome v0.14480 ATG16L1 Elena Savva Classified gene: ATG16L1 as Red List (low evidence)
Mendeliome v0.14480 ATG16L1 Elena Savva Gene: atg16l1 has been classified as Red List (Low Evidence).
Mendeliome v0.14478 ATP2A2 Elena Savva Phenotypes for gene: ATP2A2 were changed from to Acrokeratosis verruciformis MIM#101900; Darier disease MIM#124200
Mendeliome v0.14475 ATP1A1 Elena Savva Gene: atp1a1 has been classified as Green List (High Evidence).
Mendeliome v0.14474 ATL3 Elena Savva Gene: atl3 has been classified as Green List (High Evidence).
Mendeliome v0.14474 ATP2A2 Elena Savva reviewed gene: ATP2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24336169; Phenotypes: Acrokeratosis verruciformis MIM#101900, Darier disease MIM#124200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14472 ATF1 Elena Savva Gene: atf1 has been classified as Red List (Low Evidence).
Mendeliome v0.14472 ATF1 Elena Savva Classified gene: ATF1 as Red List (low evidence)
Mendeliome v0.14472 ATF1 Elena Savva Gene: atf1 has been classified as Red List (Low Evidence).
Mendeliome v0.14471 MEIOB Zornitza Stark Gene: meiob has been classified as Green List (High Evidence).
Mendeliome v0.14471 ASPN Elena Savva Gene: aspn has been classified as Red List (Low Evidence).
Mendeliome v0.14471 MEGF8 Zornitza Stark Gene: megf8 has been classified as Green List (High Evidence).
Mendeliome v0.14468 MEFV Zornitza Stark Gene: mefv has been classified as Green List (High Evidence).
Mendeliome v0.14465 MED23 Zornitza Stark Gene: med23 has been classified as Green List (High Evidence).
Mendeliome v0.14465 MED23 Zornitza Stark Phenotypes for gene: MED23 were changed from to Intellectual developmental disorder, autosomal recessive 18, with or without epilepsy, MIM# 614249
Mendeliome v0.14462 MED23 Zornitza Stark reviewed gene: MED23: Rating: GREEN; Mode of pathogenicity: None; Publications: 21868677, 25845469, 27311965, 30847200, 31164858; Phenotypes: Intellectual developmental disorder, autosomal recessive 18, with or without epilepsy, MIM# 614249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14462 MED13 Zornitza Stark Gene: med13 has been classified as Green List (High Evidence).
Mendeliome v0.14459 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Mendeliome v0.14456 MCM9 Zornitza Stark Gene: mcm9 has been classified as Green List (High Evidence).
Mendeliome v0.14456 MCM9 Zornitza Stark Phenotypes for gene: MCM9 were changed from to Ovarian dysgenesis 4, MIM# 616185
Mendeliome v0.14453 MCM9 Zornitza Stark reviewed gene: MCM9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25480036, 26771056, 33538981, 33095795; Phenotypes: Ovarian dysgenesis 4, MIM# 616185; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14453 MCM8 Zornitza Stark Gene: mcm8 has been classified as Green List (High Evidence).
Mendeliome v0.14452 ASPN Elena Savva Classified gene: ASPN as Red List (low evidence)
Mendeliome v0.14452 ASPN Elena Savva Gene: aspn has been classified as Red List (Low Evidence).
Mendeliome v0.14451 ARV1 Elena Savva Gene: arv1 has been classified as Green List (High Evidence).
Mendeliome v0.14445 MCM6 Zornitza Stark Gene: mcm6 has been classified as Red List (Low Evidence).
Mendeliome v0.14445 MCM6 Zornitza Stark Phenotypes for gene: MCM6 were changed from to Lactase persistence/nonpersistence 223100
Mendeliome v0.14443 MCM6 Zornitza Stark Classified gene: MCM6 as Red List (low evidence)
Mendeliome v0.14443 MCM6 Zornitza Stark Gene: mcm6 has been classified as Red List (Low Evidence).
Mendeliome v0.14442 MCM6 Zornitza Stark reviewed gene: MCM6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lactase persistence/nonpersistence 223100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14442 OAS1 Zornitza Stark Phenotypes for gene: OAS1 were changed from Autoinflammatory immunodeficiency; infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinaemia to Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042
Mendeliome v0.14441 OAS1 Zornitza Stark edited their review of gene: OAS1: Changed phenotypes: Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042
Mendeliome v0.14441 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Mendeliome v0.14438 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Green List (High Evidence).
Mendeliome v0.14435 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Green List (High Evidence).
Mendeliome v0.14432 MC3R Zornitza Stark Gene: mc3r has been classified as Red List (Low Evidence).
Mendeliome v0.14432 MC3R Zornitza Stark Phenotypes for gene: MC3R were changed from to {Obesity, severe, susceptibility to, BMIQ9} 602025
Mendeliome v0.14430 MC3R Zornitza Stark Classified gene: MC3R as Red List (low evidence)
Mendeliome v0.14430 MC3R Zornitza Stark Gene: mc3r has been classified as Red List (Low Evidence).
Mendeliome v0.14429 MC3R Zornitza Stark reviewed gene: MC3R: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Obesity, severe, susceptibility to, BMIQ9} 602025; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14429 MC2R Zornitza Stark Gene: mc2r has been classified as Green List (High Evidence).
Mendeliome v0.14429 MC2R Zornitza Stark Phenotypes for gene: MC2R were changed from to Glucocorticoid deficiency, due to ACTH unresponsiveness, MIM# 202200
Mendeliome v0.14426 MC2R Zornitza Stark reviewed gene: MC2R: Rating: GREEN; Mode of pathogenicity: None; Publications: 8094489, 8227361; Phenotypes: Glucocorticoid deficiency, due to ACTH unresponsiveness, MIM# 202200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14426 MBL2 Zornitza Stark Gene: mbl2 has been classified as Red List (Low Evidence).
Mendeliome v0.14423 MBL2 Zornitza Stark Classified gene: MBL2 as Red List (low evidence)
Mendeliome v0.14423 MBL2 Zornitza Stark Gene: mbl2 has been classified as Red List (Low Evidence).
Mendeliome v0.14422 MATR3 Zornitza Stark Gene: matr3 has been classified as Green List (High Evidence).
Mendeliome v0.14422 MATR3 Zornitza Stark Phenotypes for gene: MATR3 were changed from to Amyotrophic lateral sclerosis 21, MIM# 606070; Distal myopathy
Mendeliome v0.14419 MATR3 Zornitza Stark reviewed gene: MATR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19344878, 24686783, 35205163, 34659085, 34173818, 26493020; Phenotypes: Amyotrophic lateral sclerosis 21, MIM# 606070, Distal myopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14419 MAP3K1 Zornitza Stark Gene: map3k1 has been classified as Green List (High Evidence).
Mendeliome v0.14416 MAK Zornitza Stark Gene: mak has been classified as Green List (High Evidence).
Mendeliome v0.14413 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
Mendeliome v0.14413 MAGT1 Zornitza Stark Phenotypes for gene: MAGT1 were changed from to Congenital disorder of glycosylation, type Icc (MIM# 301031); Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853)
Mendeliome v0.14410 MAGT1 Zornitza Stark changed review comment from: PMID: 31036665;
- 3 affecteds (males; 2x CDG and 1x XMEN)
- All 3 patients have an N-glycosylation defect

PMID: 31714901;
- 23 XMEN patients from 17 families
- glycoproteomic analysis on T cells from 3 patients with XMEN showed defective glycosylation; to: PMID: 31036665;
- 3 affecteds (males; 2x CDG and 1x XMEN)
- All 3 patients have an N-glycosylation defect

PMID: 31714901;
- 23 XMEN patients from 17 families
- glycoproteomic analysis on T cells from 3 patients with XMEN showed defective glycosylation

These likely represent a single disorder.
Mendeliome v0.14410 MAGT1 Zornitza Stark reviewed gene: MAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31036665, 31714901; Phenotypes: Congenital disorder of glycosylation, type Icc (MIM# 301031), Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14410 GREM1 Krithika Murali reviewed gene: GREM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22561515, 26493165, 21128281, 29804199; Phenotypes: hereditary mixed polyposis syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14410 MSX1 Abhijit Kulkarni reviewed gene: MSX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33419968, 33708320, 32192766; Phenotypes: Witkop syndrome (Ectodermal Dysplasia) (MIM: 189500),Cleft Lip+/- Cleft Palate (Rofacial Cleft- MIM :608874), Oligodontia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14410 MAGI2 Zornitza Stark Gene: magi2 has been classified as Green List (High Evidence).
Mendeliome v0.14407 MYO3A Zornitza Stark Gene: myo3a has been classified as Green List (High Evidence).
Mendeliome v0.14407 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Green List (High Evidence).
Mendeliome v0.14407 OPHN1 Zornitza Stark Phenotypes for gene: OPHN1 were changed from to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, MIM#300486
Mendeliome v0.14404 OPHN1 Zornitza Stark commented on gene: OPHN1: OPHN1 variants cause cerebellar hypoplasia and distinctive facial appearance, macrocephaly is a feature. At least 8 families reported.
Mendeliome v0.14404 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Mendeliome v0.14404 PAH Zornitza Stark Phenotypes for gene: PAH were changed from to Phenylketonuria MIM#261600; Disorders of phenylalanine or tyrosine metabolism
Mendeliome v0.14401 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Mendeliome v0.14401 PCDH12 Zornitza Stark Phenotypes for gene: PCDH12 were changed from to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Mendeliome v0.14398 PCDH12 Zornitza Stark reviewed gene: PCDH12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27164683, 30178464; Phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14398 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Mendeliome v0.14395 PEX10 Zornitza Stark Gene: pex10 has been classified as Green List (High Evidence).
Mendeliome v0.14395 PEX10 Zornitza Stark Phenotypes for gene: PEX10 were changed from to Peroxisome biogenesis disorder 6A (Zellweger) (MIM#614870); Peroxisome biogenesis disorder 6B (MIM#614871)
Mendeliome v0.14392 PCK1 Zornitza Stark Gene: pck1 has been classified as Green List (High Evidence).
Mendeliome v0.14392 PCK1 Zornitza Stark Phenotypes for gene: PCK1 were changed from to Phosphoenolpyruvate carboxykinase deficiency, cytosolic MIM#261680; Disorders of gluconeogenesis
Mendeliome v0.14389 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Mendeliome v0.14389 REEP1 Zornitza Stark Gene: reep1 has been classified as Green List (High Evidence).
Mendeliome v0.14389 REEP1 Zornitza Stark Phenotypes for gene: REEP1 were changed from to Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250; Charcot-Marie-Tooth; severe congenital distal SMA with diaphragmatic paralysis; congenital axonal neuropathy and diaphragmatic palsy
Mendeliome v0.14386 RLBP1 Zornitza Stark Gene: rlbp1 has been classified as Green List (High Evidence).
Mendeliome v0.14383 RMND1 Zornitza Stark Gene: rmnd1 has been classified as Green List (High Evidence).
Mendeliome v0.14381 RNASEH1 Zornitza Stark Gene: rnaseh1 has been classified as Green List (High Evidence).
Mendeliome v0.14381 RNASEH1 Zornitza Stark Phenotypes for gene: RNASEH1 were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 MIM#616479
Mendeliome v0.14379 RBFOX2 Chern Lim edited their review of gene: RBFOX2: Added comment: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.; Changed publications: PMID: 26785492, 27670201, 27485310, 25205790, 35137168, 26785492
Mendeliome v0.14378 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Mendeliome v0.14375 RNF139 Zornitza Stark Gene: rnf139 has been classified as Red List (Low Evidence).
Mendeliome v0.14372 RNF139 Zornitza Stark Classified gene: RNF139 as Red List (low evidence)
Mendeliome v0.14372 RNF139 Zornitza Stark Gene: rnf139 has been classified as Red List (Low Evidence).
Mendeliome v0.14371 RP1 Zornitza Stark Gene: rp1 has been classified as Green List (High Evidence).
Mendeliome v0.14368 RP2 Zornitza Stark Gene: rp2 has been classified as Green List (High Evidence).
Mendeliome v0.14365 RP9 Zornitza Stark Gene: rp9 has been classified as Red List (Low Evidence).
Mendeliome v0.14361 RP9 Zornitza Stark Classified gene: RP9 as Red List (low evidence)
Mendeliome v0.14361 RP9 Zornitza Stark Gene: rp9 has been classified as Red List (Low Evidence).
Mendeliome v0.14360 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Mendeliome v0.14357 SACS Zornitza Stark Gene: sacs has been classified as Green List (High Evidence).
Mendeliome v0.14355 SCN11A Zornitza Stark Gene: scn11a has been classified as Green List (High Evidence).
Mendeliome v0.14352 TMC8 Zornitza Stark Gene: tmc8 has been classified as Green List (High Evidence).
Mendeliome v0.14352 TMC8 Zornitza Stark Phenotypes for gene: TMC8 were changed from to Epidermodysplasia verruciformis 2, MIM# 618231
Mendeliome v0.14349 TMC8 Zornitza Stark reviewed gene: TMC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 12426567, 28646613; Phenotypes: Epidermodysplasia verruciformis 2, MIM# 618231; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14348 ATP6V0A1 Bryony Thompson Classified gene: ATP6V0A1 as Green List (high evidence)
Mendeliome v0.14348 ATP6V0A1 Bryony Thompson Gene: atp6v0a1 has been classified as Green List (High Evidence).
Mendeliome v0.14345 RBFOX2 Chern Lim gene: RBFOX2 was added
gene: RBFOX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBFOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX2 were set to PMID: 26785492; 27670201; 27485310; 25205790; 35137168
Phenotypes for gene: RBFOX2 were set to Hypoplastic left heart syndrome (HLHS)
Review for gene: RBFOX2 was set to AMBER
gene: RBFOX2 was marked as current diagnostic
Added comment: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS).
No further patient-specific clinical or variant info were available.

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Sources: Literature
Mendeliome v0.14345 GRIA4 Ain Roesley Gene: gria4 has been classified as Green List (High Evidence).
Mendeliome v0.14344 GRID2 Ain Roesley Gene: grid2 has been classified as Green List (High Evidence).
Mendeliome v0.14344 GRID2 Ain Roesley Phenotypes for gene: GRID2 were changed from to Spinocerebellar ataxia, autosomal recessive 18 MIM#616204
Mendeliome v0.14343 GRID2 Ain Roesley reviewed gene: GRID2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32622959, 32170608; Phenotypes: Spinocerebellar ataxia, autosomal recessive 18 MIM#616204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14343 GRIN2D Ain Roesley Gene: grin2d has been classified as Green List (High Evidence).
Mendeliome v0.14341 TMC8 Abhijit Kulkarni reviewed gene: TMC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 34459021, 28646613; Phenotypes: Epidermodysplasia verruciformis 2 (MIM: 61831); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14341 BICC1 Abhijit Kulkarni reviewed gene: BICC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: renal dysplasia, cystic, susceptibility to; Mode of inheritance: None
Mendeliome v0.14341 UGT1A1 Zornitza Stark Gene: ugt1a1 has been classified as Green List (High Evidence).
Mendeliome v0.14339 UNC13D Zornitza Stark Gene: unc13d has been classified as Green List (High Evidence).
Mendeliome v0.14339 UNG Zornitza Stark Gene: ung has been classified as Green List (High Evidence).
Mendeliome v0.14337 UQCC2 Zornitza Stark Gene: uqcc2 has been classified as Green List (High Evidence).
Mendeliome v0.14334 UQCRB Zornitza Stark Gene: uqcrb has been classified as Green List (High Evidence).
Mendeliome v0.14331 UROD Zornitza Stark Gene: urod has been classified as Green List (High Evidence).
Mendeliome v0.14328 MAGED2 Zornitza Stark Gene: maged2 has been classified as Green List (High Evidence).
Mendeliome v0.14328 MAGED2 Zornitza Stark Phenotypes for gene: MAGED2 were changed from to Bartter syndrome, type 5, antenatal, transient, MIM# 300971
Mendeliome v0.14325 MAGED2 Zornitza Stark reviewed gene: MAGED2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27120771; Phenotypes: Bartter syndrome, type 5, antenatal, transient, MIM# 300971; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14325 MRPS2 Zornitza Stark Gene: mrps2 has been classified as Green List (High Evidence).
Mendeliome v0.14322 MSH3 Zornitza Stark Gene: msh3 has been classified as Green List (High Evidence).
Mendeliome v0.14322 MSH3 Zornitza Stark Phenotypes for gene: MSH3 were changed from to Familial adenomatous polyposis 4 , MIM#617100
Mendeliome v0.14319 MSH3 Zornitza Stark reviewed gene: MSH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476653, 10706084, 34843512; Phenotypes: Familial adenomatous polyposis 4 , MIM#617100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14319 MSRB3 Zornitza Stark Gene: msrb3 has been classified as Green List (High Evidence).
Mendeliome v0.14319 MSRB3 Zornitza Stark Phenotypes for gene: MSRB3 were changed from to Deafness, autosomal recessive 74, MIM# 613718
Mendeliome v0.14316 MSRB3 Zornitza Stark reviewed gene: MSRB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19650862, 24191262, 21185009; Phenotypes: Deafness, autosomal recessive 74, MIM# 613718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14316 MTAP Zornitza Stark Gene: mtap has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14316 MTAP Zornitza Stark Phenotypes for gene: MTAP were changed from to Diaphyseal medullary stenosis with malignant fibrous histiocytoma, MIM# 112250
Mendeliome v0.14313 MTAP Zornitza Stark Classified gene: MTAP as Amber List (moderate evidence)
Mendeliome v0.14313 MTAP Zornitza Stark Gene: mtap has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14312 MTAP Zornitza Stark reviewed gene: MTAP: Rating: AMBER; Mode of pathogenicity: None; Publications: 22464254; Phenotypes: Diaphyseal medullary stenosis with malignant fibrous histiocytoma, MIM# 112250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14312 MTFMT Zornitza Stark Gene: mtfmt has been classified as Green List (High Evidence).
Mendeliome v0.14309 MTHFD1 Zornitza Stark Gene: mthfd1 has been classified as Green List (High Evidence).
Mendeliome v0.14305 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Mendeliome v0.14302 MTM1 Zornitza Stark Gene: mtm1 has been classified as Green List (High Evidence).
Mendeliome v0.14299 MTO1 Zornitza Stark Gene: mto1 has been classified as Green List (High Evidence).
Mendeliome v0.14295 MTOR Zornitza Stark Gene: mtor has been classified as Green List (High Evidence).
Mendeliome v0.14295 MTOR Zornitza Stark Phenotypes for gene: MTOR were changed from to Smith-Kingsmore syndrome, MIM# 616638; Focal cortical dysplasia, type II, somatic, MIM# 607341; Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Mendeliome v0.14292 MTOR Zornitza Stark reviewed gene: MTOR: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28892148, 25878179, 26018084; Phenotypes: Smith-Kingsmore syndrome, MIM# 616638, Focal cortical dysplasia, type II, somatic, MIM# 607341, Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14291 DNAJC5 Krithika Murali reviewed gene: DNAJC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22978711, 21820099, 22235333, 31919451, 26659577; Phenotypes: Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant - MIM#162350, ceroid lipofuscinosis, neuronal, 4 (Kufs type) - MONDO:0008083; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14291 DNM1L Krithika Murali reviewed gene: DNM1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR), Optic atrophy 5 - MIM#610708 (AD); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14291 DSCAM Krithika Murali edited their review of gene: DSCAM: Added comment: No OMIM gene disease association. Variants predominantly identified from large cohort studies with limited phenotypic information. Associations with ID, ASD, Hirschsprung disease reported. One homozygous splice site variant reported with no parental phenotypes provided.

PMID 34253863 Lim et al 2021 - 12 yo proband with severe autism spectrum disorder diagnosed age 3, de novo heterozygous c.2051 del p.(L684X) variant identified (absent from gnomAD). Skin fibroblast human iPSC cells generated from proband and healthy controls. Forebrain-like induced neuronal cells showed reduced mRNA expression for NMDA-R subunits.

PMID 28600779 Monies et al 2017 - Homozygous splice site variant identified in proband from consanguineous Saudi family. Proband had growth restriction, microcephaly, developmental delay. Parental phenotype not provided.

PMID 30095639 and PMID 23671607 - report association between DSCAM polymorphisms and Hirschsprung disease in Chinese and European populations.

PMID 27824329 Wang et al 2016 - 2 denovo mutations in mixed ID/ASD cohort of 1,045; including comparison of previously published cases 6 LOF out of 4,998 cases.

PMID 28191889 2 denovo LOF in 13,407 mixed ID/ASD cases plus 4 previosly published cases our ot 6158; conclude denovo LOF enriched in cases vs controls

PMID 21904980; mouse model – het LOF mice show hydrocephalus, decreased motor function and impaired motor learning ability,

Evidence for missense lacking currently; Changed publications: 34253863, 32807774, 28600779, 21904980, 28191889, 27824329, 30095639, 23671607
Mendeliome v0.14291 MTTP Zornitza Stark Gene: mttp has been classified as Green List (High Evidence).
Mendeliome v0.14288 MUT Zornitza Stark Gene: mut has been classified as Green List (High Evidence).
Mendeliome v0.14285 MVK Zornitza Stark Gene: mvk has been classified as Green List (High Evidence).
Mendeliome v0.14282 MXI1 Zornitza Stark Gene: mxi1 has been classified as Red List (Low Evidence).
Mendeliome v0.14282 MXI1 Zornitza Stark Classified gene: MXI1 as Red List (low evidence)
Mendeliome v0.14282 MXI1 Zornitza Stark Gene: mxi1 has been classified as Red List (Low Evidence).
Mendeliome v0.14281 MYD88 Zornitza Stark Gene: myd88 has been classified as Green List (High Evidence).
Mendeliome v0.14278 MYH14 Zornitza Stark Gene: myh14 has been classified as Green List (High Evidence).
Mendeliome v0.14275 MYH3 Zornitza Stark Gene: myh3 has been classified as Green List (High Evidence).
Mendeliome v0.14275 MYH3 Zornitza Stark Phenotypes for gene: MYH3 were changed from to Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469
Mendeliome v0.14272 MYH3 Zornitza Stark reviewed gene: MYH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25957469, 26544689, 21531865, 18695058; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436, Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110, Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14272 MYO1E Zornitza Stark Gene: myo1e has been classified as Green List (High Evidence).
Mendeliome v0.14272 MYO1E Zornitza Stark Phenotypes for gene: MYO1E were changed from to Glomerulosclerosis, focal segmental, 6, MIM# 614131
Mendeliome v0.14269 MYO1E Zornitza Stark reviewed gene: MYO1E: Rating: GREEN; Mode of pathogenicity: None; Publications: 21756023, 31520189, 25739341, 23977349; Phenotypes: Glomerulosclerosis, focal segmental, 6, MIM# 614131; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14269 WNT1 Zornitza Stark Gene: wnt1 has been classified as Green List (High Evidence).
Mendeliome v0.14269 WNT1 Zornitza Stark Phenotypes for gene: WNT1 were changed from to Osteogenesis imperfecta, type XV, MIM# 615220
Mendeliome v0.14266 WNT1 Zornitza Stark reviewed gene: WNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23499309, 23499310, 23656646, 26671912; Phenotypes: Osteogenesis imperfecta, type XV, MIM# 615220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14266 WNK4 Zornitza Stark Gene: wnk4 has been classified as Green List (High Evidence).
Mendeliome v0.14263 WNK1 Zornitza Stark Gene: wnk1 has been classified as Green List (High Evidence).
Mendeliome v0.14260 WDR4 Zornitza Stark Gene: wdr4 has been classified as Green List (High Evidence).
Mendeliome v0.14257 WDR36 Zornitza Stark Classified gene: WDR36 as Amber List (moderate evidence)
Mendeliome v0.14257 WDR36 Zornitza Stark Gene: wdr36 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14256 WDR36 Zornitza Stark Gene: wdr36 has been classified as Green List (High Evidence).
Mendeliome v0.14253 WASHC5 Zornitza Stark Gene: washc5 has been classified as Green List (High Evidence).
Mendeliome v0.14250 WASF1 Zornitza Stark Gene: wasf1 has been classified as Green List (High Evidence).
Mendeliome v0.14247 WAC Zornitza Stark Gene: wac has been classified as Green List (High Evidence).
Mendeliome v0.14244 RNASEH1 Belinda Chong reviewed gene: RNASEH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26094573, 31258551; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 MIM#616479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14244 FXYD2 Bryony Thompson Gene: fxyd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14240 FXYD2 Bryony Thompson Classified gene: FXYD2 as Amber List (moderate evidence)
Mendeliome v0.14240 FXYD2 Bryony Thompson Gene: fxyd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14239 RIPPLY2 Zornitza Stark Gene: ripply2 has been classified as Green List (High Evidence).
Mendeliome v0.14239 RIPPLY2 Zornitza Stark Phenotypes for gene: RIPPLY2 were changed from to Spondylocostal dysostosis 6, MIM# 616566
Mendeliome v0.14236 RIPPLY2 Zornitza Stark reviewed gene: RIPPLY2: Rating: ; Mode of pathogenicity: None; Publications: 25343988, 33410135, 32212228, 29761784; Phenotypes: Spondylocostal dysostosis 6, MIM# 616566; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14236 FXN Bryony Thompson Gene: fxn has been classified as Green List (High Evidence).
Mendeliome v0.14236 MYOC Zornitza Stark Gene: myoc has been classified as Green List (High Evidence).
Mendeliome v0.14232 MYOCD Zornitza Stark changed review comment from: Congenital megabladder (MGBL) is characterized by a massively dilated bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, likely the result of differences in urethra and bladder development and length differences in urethra between males and females.

Seven affected males from three families. Five females and one male with the variant were unaffected, suggesting incomplete penetrance.

Additional family in PMID 35005812 as part of a large prenatal renal cohort.; to: Congenital megabladder (MGBL) is characterized by a massively dilated bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, likely the result of differences in urethra and bladder development and length differences in urethra between males and females.

Seven affected males from three families. Five females and one male with the variant were unaffected, suggesting incomplete penetrance.

Additional family in PMID 35005812 as part of a large prenatal renal cohort.

Mono allelic disease in males (megabladder), bi-allelic disease in males and females (megabladder and congenital heart disease).

Mouse models.
Mendeliome v0.14232 MYOCD Zornitza Stark Gene: myocd has been classified as Green List (High Evidence).
Mendeliome v0.14229 MYOT Zornitza Stark Gene: myot has been classified as Green List (High Evidence).
Mendeliome v0.14223 FXN Bryony Thompson edited their review of gene: FXN: Added comment: Well-established gene-disease association. 96% of cases are caused by biallelic intronic GAA triplet repeat expansion and 4% are attributable to biallelic single nucleotide variants and small indels. Loss of function is the mechanism of disease.; Changed rating: GREEN; Changed publications: 20301458, 26704351; Changed phenotypes: Friedreich ataxia MONDO:0100339; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Set current diagnostic: yes
Mendeliome v0.14223 FUT8 Bryony Thompson Gene: fut8 has been classified as Green List (High Evidence).
Mendeliome v0.14220 FUT1 Bryony Thompson Gene: fut1 has been classified as Red List (Low Evidence).
Mendeliome v0.14219 FUT1 Bryony Thompson Classified gene: FUT1 as Red List (low evidence)
Mendeliome v0.14219 FUT1 Bryony Thompson Added comment: Comment on list classification: Biallelic loss of function variants produce the Bombay blood group, which is a recessive H-deficient red blood cell phenotype. Bombay and para-Bombay individuals display no apparent deleterious phenotype except in circumstances requiring blood transfusion. No evidence for Mendelian disease associated with this gene.
Mendeliome v0.14219 FUT1 Bryony Thompson Gene: fut1 has been classified as Red List (Low Evidence).
Mendeliome v0.14217 FUT1 Bryony Thompson Classified gene: FUT1 as Red List (low evidence)
Mendeliome v0.14217 FUT1 Bryony Thompson Added comment: Comment on list classification: Biallelic loss of function variants cause Bombay phenotype, which is a recessive H-deficient red blood cell phenotype. Bombay and para-Bombay individuals display no apparent deleterious phenotype except in circumstances requiring blood transfusion. No evidence for Mendelian disease associated with this gene.
Mendeliome v0.14217 FUT1 Bryony Thompson Gene: fut1 has been classified as Red List (Low Evidence).
Mendeliome v0.14215 FSHR Bryony Thompson Gene: fshr has been classified as Green List (High Evidence).
Mendeliome v0.14215 FTO Bryony Thompson Gene: fto has been classified as Green List (High Evidence).
Mendeliome v0.14212 RIMS1 Zornitza Stark Gene: rims1 has been classified as Green List (High Evidence).
Mendeliome v0.14209 RHEB Zornitza Stark Gene: rheb has been classified as Green List (High Evidence).
Mendeliome v0.14209 FSHR Bryony Thompson Phenotypes for gene: FSHR were changed from to Ovarian dysgenesis 1 MONDO:0024463; Ovarian hyperstimulation syndrome MONDO:0011972
Mendeliome v0.14208 RHEB Zornitza Stark Phenotypes for gene: RHEB were changed from to Neurodevelopmental disorder MONDO:0700092, RHEB-related; Intellectual disability; Macrocephaly; Focal cortical dysplasia
Mendeliome v0.14205 RHEB Zornitza Stark reviewed gene: RHEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31337748, 29051493; Phenotypes: Neurodevelopmental disorder MONDO:0700092, RHEB-related, Intellectual disability, Macrocephaly, Focal cortical dysplasia; Mode of inheritance: Other
Mendeliome v0.14203 FSHR Bryony Thompson reviewed gene: FSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16630814, 7553856, 9020851, 9769327, 20087398, 9854118, 12930928, 12930927, 17721928, 26911863; Phenotypes: Ovarian dysgenesis 1 MONDO:0024463, Ovarian hyperstimulation syndrome MONDO:0011972; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14203 RHCE Zornitza Stark Gene: rhce has been classified as Green List (High Evidence).
Mendeliome v0.14200 RGS9BP Zornitza Stark Gene: rgs9bp has been classified as Green List (High Evidence).
Mendeliome v0.14200 RGS9BP Zornitza Stark Phenotypes for gene: RGS9BP were changed from to Bradyopsia, MIM# 608415
Mendeliome v0.14197 RGS9BP Zornitza Stark reviewed gene: RGS9BP: Rating: GREEN; Mode of pathogenicity: None; Publications: 14702087, 19818506; Phenotypes: Bradyopsia, MIM# 608415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14197 RGS9 Zornitza Stark Gene: rgs9 has been classified as Green List (High Evidence).
Mendeliome v0.14197 RGS9 Zornitza Stark Phenotypes for gene: RGS9 were changed from to Bradyopsia, MIM# 608415
Mendeliome v0.14194 RGS9 Zornitza Stark reviewed gene: RGS9: Rating: GREEN; Mode of pathogenicity: None; Publications: 14702087, 10676965, 19818506; Phenotypes: Bradyopsia, MIM# 608415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14194 RFX6 Zornitza Stark Gene: rfx6 has been classified as Green List (High Evidence).
Mendeliome v0.14192 SEMA7A Zornitza Stark Phenotypes for gene: SEMA7A were changed from Decreased bone mineral density; Kallmann syndrome; progressive familial intrahepatic cholestasis to Decreased bone mineral density; Kallmann syndrome; Cholestasis, progressive familial intrahepatic, 11 , MIM# 619874
Mendeliome v0.14191 SEMA7A Zornitza Stark edited their review of gene: SEMA7A: Changed rating: AMBER; Changed phenotypes: Cholestasis, progressive familial intrahepatic, 11 , MIM# 619874; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14191 FXYD6 Bryony Thompson Gene: fxyd6 has been classified as Red List (Low Evidence).
Mendeliome v0.14189 FXYD6 Bryony Thompson Classified gene: FXYD6 as Red List (low evidence)
Mendeliome v0.14189 FXYD6 Bryony Thompson Gene: fxyd6 has been classified as Red List (Low Evidence).
Mendeliome v0.14188 FZD2 Bryony Thompson Gene: fzd2 has been classified as Green List (High Evidence).
Mendeliome v0.14188 FZD2 Bryony Thompson Phenotypes for gene: FZD2 were changed from to Autosomal dominant omodysplasia MONDO:0008123
Mendeliome v0.14186 FBP2 Zornitza Stark Gene: fbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14186 FBP2 Zornitza Stark Classified gene: FBP2 as Amber List (moderate evidence)
Mendeliome v0.14186 FBP2 Zornitza Stark Gene: fbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14185 FBP2 Zornitza Stark gene: FBP2 was added
gene: FBP2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBP2 were set to 33977262
Phenotypes for gene: FBP2 were set to Leukodystrophy, childhood-onset, remitting, MIM# 619864
Review for gene: FBP2 was set to AMBER
Added comment: 8 individuals from 3 generations in a single family reported with a variant in this gene. The children presented with episode of regression and leukodystrophy in early childhood, from which they made a slow recovery. The adults had a broad range of neurobehavioural phenotypes but also had leukodystrophy on imaging. Some functional data presented (in vitro).
Sources: Expert list
Mendeliome v0.14181 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14181 MOV10L1 Zornitza Stark Classified gene: MOV10L1 as Amber List (moderate evidence)
Mendeliome v0.14181 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14178 RFC2 Zornitza Stark Gene: rfc2 has been classified as Red List (Low Evidence).
Mendeliome v0.14178 RFC2 Zornitza Stark Classified gene: RFC2 as Red List (low evidence)
Mendeliome v0.14178 RFC2 Zornitza Stark Gene: rfc2 has been classified as Red List (Low Evidence).
Mendeliome v0.14177 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Mendeliome v0.14177 REST Zornitza Stark Phenotypes for gene: REST were changed from to Deafness, autosomal dominant 27, MIM# 612431; {Wilms tumor 6, susceptibility to}, MIM# 616806; Fibromatosis, gingival, 5, MIM# 617626
Mendeliome v0.14174 REST Zornitza Stark reviewed gene: REST: Rating: GREEN; Mode of pathogenicity: None; Publications: 29961578, 34828371, 26551668, 28686854; Phenotypes: Deafness, autosomal dominant 27, MIM# 612431, {Wilms tumor 6, susceptibility to}, MIM# 616806, Fibromatosis, gingival, 5, MIM# 617626; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14174 REEP6 Zornitza Stark Gene: reep6 has been classified as Green List (High Evidence).
Mendeliome v0.14171 RCBTB1 Zornitza Stark Gene: rcbtb1 has been classified as Green List (High Evidence).
Mendeliome v0.14167 FZD2 Bryony Thompson reviewed gene: FZD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25759469, 30455931, 29383834, 29230162; Phenotypes: Autosomal dominant omodysplasia MONDO:0008123; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14167 FSHB Bryony Thompson Gene: fshb has been classified as Green List (High Evidence).
Mendeliome v0.14164 FRZB Bryony Thompson Gene: frzb has been classified as Red List (Low Evidence).
Mendeliome v0.14163 FRRS1L Bryony Thompson Gene: frrs1l has been classified as Green List (High Evidence).
Mendeliome v0.14161 FRZB Bryony Thompson Classified gene: FRZB as Red List (low evidence)
Mendeliome v0.14161 FRZB Bryony Thompson Gene: frzb has been classified as Red List (Low Evidence).
Mendeliome v0.14158 FOXN1 Bryony Thompson Gene: foxn1 has been classified as Green List (High Evidence).
Mendeliome v0.14158 RBPJ Zornitza Stark Gene: rbpj has been classified as Green List (High Evidence).
Mendeliome v0.14152 FOXI1 Bryony Thompson Gene: foxi1 has been classified as Green List (High Evidence).
Mendeliome v0.14152 FOXI1 Bryony Thompson Phenotypes for gene: FOXI1 were changed from to autosomal recessive distal renal tubular acidosis MONDO:0018440
Mendeliome v0.14149 FOXI1 Bryony Thompson reviewed gene: FOXI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843211, 12642503, 29242249, 17503324, 30268946, 27997596, 22285650, 23965030, 24860705, 32447495, 19204907; Phenotypes: autosomal recessive distal renal tubular acidosis MONDO:0018440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14149 FOXD3 Bryony Thompson Gene: foxd3 has been classified as Red List (Low Evidence).
Mendeliome v0.14147 FOXD3 Bryony Thompson Classified gene: FOXD3 as Red List (low evidence)
Mendeliome v0.14147 FOXD3 Bryony Thompson Gene: foxd3 has been classified as Red List (Low Evidence).
Mendeliome v0.14146 FMR1 Bryony Thompson Gene: fmr1 has been classified as Green List (High Evidence).
Mendeliome v0.14145 RBP3 Zornitza Stark Gene: rbp3 has been classified as Green List (High Evidence).
Mendeliome v0.14142 RBM28 Zornitza Stark Gene: rbm28 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14139 RBM28 Zornitza Stark Classified gene: RBM28 as Amber List (moderate evidence)
Mendeliome v0.14139 RBM28 Zornitza Stark Gene: rbm28 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14138 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Green List (High Evidence).
Mendeliome v0.14135 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Mendeliome v0.14134 SCN2A Zornitza Stark changed review comment from: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including ataxia.; to: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including ataxia. Rather than being discrete disorders, these probably represent a continuum of manifestations of a single brain channelopathy disorder.

Multiple families reported.
Mendeliome v0.14131 SCN9A Zornitza Stark Gene: scn9a has been classified as Green List (High Evidence).
Mendeliome v0.14131 SCN9A Zornitza Stark Phenotypes for gene: SCN9A were changed from to Erythermalgia, primary, MIM# 133020; Insensitivity to pain, congenital, MIM# 243000; Neuropathy, hereditary sensory and autonomic, type IID, MIM# 243000; Paroxysmal extreme pain disorder, MIM# 167400; Small fiber neuropathy,MIM# 133020
Mendeliome v0.14129 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Green List (High Evidence).
Mendeliome v0.14126 SLC22A12 Zornitza Stark Gene: slc22a12 has been classified as Green List (High Evidence).
Mendeliome v0.14123 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Mendeliome v0.14119 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14116 SLC1A1 Zornitza Stark Classified gene: SLC1A1 as Amber List (moderate evidence)
Mendeliome v0.14116 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14115 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Mendeliome v0.14115 SLC19A3 Zornitza Stark Phenotypes for gene: SLC19A3 were changed from to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483
Mendeliome v0.14112 SLC19A3 Zornitza Stark reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15871139, 20065143, 23482991, 24878502, 23589815, 24166474, 26975589, 27896110; Phenotypes: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14112 SLC17A8 Zornitza Stark Gene: slc17a8 has been classified as Green List (High Evidence).
Mendeliome v0.14109 SLC17A3 Zornitza Stark Gene: slc17a3 has been classified as Red List (Low Evidence).
Mendeliome v0.14106 SLC17A3 Zornitza Stark Classified gene: SLC17A3 as Red List (low evidence)
Mendeliome v0.14106 SLC17A3 Zornitza Stark Gene: slc17a3 has been classified as Red List (Low Evidence).
Mendeliome v0.14105 SLC16A1 Zornitza Stark Gene: slc16a1 has been classified as Green List (High Evidence).
Mendeliome v0.14102 SLC11A2 Zornitza Stark Gene: slc11a2 has been classified as Green List (High Evidence).
Mendeliome v0.14099 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Mendeliome v0.14096 SGCG Zornitza Stark Gene: sgcg has been classified as Green List (High Evidence).
Mendeliome v0.14096 SGCG Zornitza Stark Phenotypes for gene: SGCG were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700; autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Mendeliome v0.14092 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Mendeliome v0.14091 FLNC Bryony Thompson Gene: flnc has been classified as Green List (High Evidence).
Mendeliome v0.14085 FLNB Bryony Thompson edited their review of gene: FLNB: Changed phenotypes: spondylocarpotarsal synostosis syndrome MONDO:0010094, filamin-related bone disorder MONDO:0019690
Mendeliome v0.14085 FLNB Bryony Thompson Phenotypes for gene: FLNB were changed from spondylocarpotarsal synostosis syndrome MONDO:0010094; osteochondrodysplasia MONDO:0005516 to spondylocarpotarsal synostosis syndrome MONDO:0010094; filamin-related bone disorder MONDO:0019690
Mendeliome v0.14084 FLNB Bryony Thompson Gene: flnb has been classified as Green List (High Evidence).
Mendeliome v0.14084 FLNB Bryony Thompson Phenotypes for gene: FLNB were changed from to spondylocarpotarsal synostosis syndrome MONDO:0010094; osteochondrodysplasia MONDO:0005516
Mendeliome v0.14081 FLNB Bryony Thompson reviewed gene: FLNB: Rating: GREEN; Mode of pathogenicity: None; Publications: 14991055, 17360453, 20301736, 29566257, 16801345, 22190451; Phenotypes: spondylocarpotarsal synostosis syndrome MONDO:0010094, osteochondrodysplasia MONDO:0005516; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14081 FLI1 Bryony Thompson Gene: fli1 has been classified as Green List (High Evidence).
Mendeliome v0.14078 FLG Bryony Thompson Gene: flg has been classified as Green List (High Evidence).
Mendeliome v0.14078 ASS1 Elena Savva Gene: ass1 has been classified as Green List (High Evidence).
Mendeliome v0.14078 FLG Bryony Thompson Phenotypes for gene: FLG were changed from to Ichthyosis vulgaris MONDO:0024304
Mendeliome v0.14074 ASTN1 Elena Savva Gene: astn1 has been classified as Green List (High Evidence).
Mendeliome v0.14072 FLG Bryony Thompson reviewed gene: FLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 16444271, 19349982, 34608691; Phenotypes: Ichthyosis vulgaris MONDO:0024304; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14070 FKTN Bryony Thompson Gene: fktn has been classified as Green List (High Evidence).
Mendeliome v0.14067 GSN Zornitza Stark Gene: gsn has been classified as Green List (High Evidence).
Mendeliome v0.14067 GSN Zornitza Stark Phenotypes for gene: GSN were changed from to Amyloidosis, Finnish type, MIM# 105120
Mendeliome v0.14064 GSN Zornitza Stark changed review comment from: The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported.

Multiple families with same founder variant.; to: The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported.

Multiple families with same founder variant, p.Asp187Asn, though other variants also reported.
Mendeliome v0.14064 GSN Zornitza Stark reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 2176164; Phenotypes: Amyloidosis, Finnish type, MIM# 105120; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14064 GSS Zornitza Stark Gene: gss has been classified as Green List (High Evidence).
Mendeliome v0.14061 GTF3C3 Zornitza Stark Gene: gtf3c3 has been classified as Green List (High Evidence).
Mendeliome v0.14058 GUCA1A Zornitza Stark Gene: guca1a has been classified as Green List (High Evidence).
Mendeliome v0.14054 ASB10 Elena Savva Gene: asb10 has been classified as Red List (Low Evidence).
Mendeliome v0.14054 ASB10 Elena Savva Classified gene: ASB10 as Red List (low evidence)
Mendeliome v0.14054 ASB10 Elena Savva Gene: asb10 has been classified as Red List (Low Evidence).
Mendeliome v0.14053 FKRP Bryony Thompson Gene: fkrp has been classified as Green List (High Evidence).
Mendeliome v0.14048 ART4 Elena Savva Gene: art4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14048 ART4 Elena Savva Classified gene: ART4 as Amber List (moderate evidence)
Mendeliome v0.14048 ART4 Elena Savva Gene: art4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14047 FHL1 Bryony Thompson Gene: fhl1 has been classified as Green List (High Evidence).
Mendeliome v0.14045 ASPA Elena Savva Gene: aspa has been classified as Green List (High Evidence).
Mendeliome v0.14040 ARMS2 Elena Savva Classified gene: ARMS2 as Red List (low evidence)
Mendeliome v0.14040 ARMS2 Elena Savva Gene: arms2 has been classified as Red List (Low Evidence).
Mendeliome v0.14039 ARMS2 Elena Savva Gene: arms2 has been classified as Green List (High Evidence).
Mendeliome v0.14038 ASH1L Elena Savva Gene: ash1l has been classified as Green List (High Evidence).
Mendeliome v0.14035 ARL2BP Elena Savva Gene: arl2bp has been classified as Green List (High Evidence).
Mendeliome v0.14035 ARL2BP Elena Savva Phenotypes for gene: ARL2BP were changed from to Retinitis pigmentosa with or without situs inversus MIM#615434
Mendeliome v0.14034 ARL2BP Elena Savva reviewed gene: ARL2BP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa with or without situs inversus MIM#615434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14034 FH Bryony Thompson Gene: fh has been classified as Green List (High Evidence).
Mendeliome v0.14034 FH Bryony Thompson Phenotypes for gene: FH were changed from to hereditary leiomyomatosis and renal cell cancer MONDO:0007888; fumaric aciduria MONDO:0011730
Mendeliome v0.14031 FH Bryony Thompson changed review comment from: Well established gene-disease associations. Loss of function is the mechanism of disease. Monoallelic variants associated with decreased fumarate hydratase enzyme activity cause FH tumour predisposition syndrome (also known as HLRCC; PMID: 11865300, 28300276). FH deficiency (also known as fumarase deficiency or fumaric aciduria) caused by biallelic variants results in severe neonatal and early infantile encephalopathy (PMID: 8200987, 20549362, 31746132). FH encodes for both mitochondrial and cytosolic FH enzyme isoforms, which catalyze hydration of fumarate to malate.; to: Well established gene-disease associations. Loss of function is the mechanism of disease. Monoallelic variants associated with decreased fumarate hydratase enzyme activity cause FH tumour predisposition syndrome (also known as HLRCC; PMID: 11865300, 28300276, 20301430). FH deficiency (also known as fumarase deficiency or fumaric aciduria) caused by biallelic variants results in severe neonatal and early infantile encephalopathy (PMID: 8200987, 20549362, 31746132, 20301679). FH encodes for both mitochondrial and cytosolic FH enzyme isoforms, which catalyze hydration of fumarate to malate.
Mendeliome v0.14031 FH Bryony Thompson reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: 11865300, 28300276, 8200987, 20549362, 31746132; Phenotypes: hereditary leiomyomatosis and renal cell cancer MONDO:0007888, fumaric aciduria MONDO:0011730; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14031 ARID1B Elena Savva Phenotypes for gene: ARID1B were changed from to Coffin-Siris syndrome 1 MIM#135900
Mendeliome v0.14030 ARID1B Elena Savva Gene: arid1b has been classified as Green List (High Evidence).
Mendeliome v0.14029 ARID1B Elena Savva reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome 1 MIM#135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14029 FGG Bryony Thompson Gene: fgg has been classified as Green List (High Evidence).
Mendeliome v0.14025 ARHGEF18 Elena Savva Gene: arhgef18 has been classified as Green List (High Evidence).
Mendeliome v0.14024 FGFR3 Bryony Thompson Phenotypes for gene: FGFR3 were changed from achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833 to achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504
Mendeliome v0.14020 FGFR3 Bryony Thompson changed review comment from: FGFR3 has many well-established gene-disease associations with various skeletal dysplasia phenotypes. Gain-of-function is the main mechanism of disease for these disorders, except camptodactyly-tall stature-scoliosis-hearing loss syndrome where bialellic loss-of-function is the expected mechanism of disease. Specific monoallelic variants cause different phenotypes: >99% achondroplasia is caused by variants leading to the missense change p.Gly380Arg; Cysteine substitutions and stop-loss protein elongation variants are highly specific for Thanatophoric dysplasia (TD) type 1; p.Lys650Glu is associated with TD type 2; p.Ala391Glu causes Crouzon syndrome with acanthosis nigricans; and p.Pro250Arg causes Muenke syndrome.; to: FGFR3 has many well-established gene-disease associations with various skeletal dysplasia phenotypes. Gain-of-function is the main mechanism of disease for these disorders, except camptodactyly-tall stature-scoliosis-hearing loss syndrome (CATSHL syndrome, see separate curation below). Specific monoallelic variants cause different phenotypes: >99% achondroplasia is caused by variants leading to the missense change p.Gly380Arg; Cysteine substitutions and stop-loss protein elongation variants are highly specific for Thanatophoric dysplasia (TD) type 1; p.Lys650Glu is associated with TD type 2; p.Ala391Glu causes Crouzon syndrome with acanthosis nigricans; and p.Pro250Arg causes Muenke syndrome.
Moderate evidence for CATSHL syndrome, AD & AR: PMID: 8630492, 17033969, 27139183, 24864036, 32641982 - 2 apparently unrelated families segregating the same missense, p.Arg621His. One consanguineous family with 2 affected brothers with homozygous p.Thr546Lys. Heterozygous individuals in the family were unaffected. No functional assays were conducted for either missense to demonstrate loss of function. Null mouse and zebrafish models are similar to the human CATSHL syndrome phenotype.
Mendeliome v0.14020 GUCA1B Zornitza Stark changed review comment from: Single founder variant identified in several Japanese individuals.; to: Single founder variant identified in several Japanese individuals.

No other P/LP variants in ClinVar.
Mendeliome v0.14020 GUCA1B Zornitza Stark Gene: guca1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14017 GUCA1B Zornitza Stark Classified gene: GUCA1B as Amber List (moderate evidence)
Mendeliome v0.14017 GUCA1B Zornitza Stark Gene: guca1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14016 FGFR3 Bryony Thompson edited their review of gene: FGFR3: Changed mode of pathogenicity: Other; Changed publications: 8630492, 32641982, 27139183, 24864036, 17033969, 20301331, 20301540, 20301650, 20301628; Changed phenotypes: achondroplasia MONDO:0007037, Thanatophoric dysplasia type 1 MONDO:0008546, Thanatophoric dysplasia type 2 MONDO:0008547, hypochondroplasia MONDO:0007793, Muenke syndrome MONDO:0011274, FGFR3-related chondrodysplasia MONDO:0019685, severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658, Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833, camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14016 GUCY1A3 Zornitza Stark Gene: gucy1a3 has been classified as Green List (High Evidence).
Mendeliome v0.14016 GUCY1A3 Zornitza Stark Phenotypes for gene: GUCY1A3 were changed from to Moyamoya 6 with achalasia, MIM# 615750
Mendeliome v0.14013 GUCY1A3 Zornitza Stark reviewed gene: GUCY1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24581742, 26777256, 34381413, 33109895; Phenotypes: Moyamoya 6 with achalasia, MIM# 615750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14013 GYG1 Zornitza Stark Gene: gyg1 has been classified as Green List (High Evidence).
Mendeliome v0.14010 GUCY2D Zornitza Stark Gene: gucy2d has been classified as Green List (High Evidence).
Mendeliome v0.14010 GUCY2D Zornitza Stark Phenotypes for gene: GUCY2D were changed from to Cone-rod dystrophy 6, MIM# 601777; Leber congenital amaurosis 1, MIM# 204000; Night blindness, congenital stationary, type 1I, MIM# 618555
Mendeliome v0.14007 GUCY2D Zornitza Stark reviewed gene: GUCY2D: Rating: GREEN; Mode of pathogenicity: None; Publications: 35314386, 35205358; Phenotypes: Cone-rod dystrophy 6, MIM# 601777, Leber congenital amaurosis 1, MIM# 204000, Night blindness, congenital stationary, type 1I, MIM# 618555; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14007 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Green List (High Evidence).
Mendeliome v0.14003 ARHGDIA Elena Savva Gene: arhgdia has been classified as Green List (High Evidence).
Mendeliome v0.14003 ARHGAP31 Elena Savva Gene: arhgap31 has been classified as Green List (High Evidence).
Mendeliome v0.14000 ANXA5 Elena Savva Gene: anxa5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13998 ANXA5 Elena Savva Classified gene: ANXA5 as Amber List (moderate evidence)
Mendeliome v0.13998 ANXA5 Elena Savva Gene: anxa5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13997 AR Elena Savva Gene: ar has been classified as Green List (High Evidence).
Mendeliome v0.13997 GYPA Zornitza Stark Gene: gypa has been classified as Red List (Low Evidence).
Mendeliome v0.13995 GYPA Zornitza Stark Classified gene: GYPA as Red List (low evidence)
Mendeliome v0.13995 GYPA Zornitza Stark Gene: gypa has been classified as Red List (Low Evidence).
Mendeliome v0.13994 GYPB Zornitza Stark Gene: gypb has been classified as Red List (Low Evidence).
Mendeliome v0.13992 GYPB Zornitza Stark Classified gene: GYPB as Red List (low evidence)
Mendeliome v0.13992 GYPB Zornitza Stark Gene: gypb has been classified as Red List (Low Evidence).
Mendeliome v0.13991 DSG4 Krithika Murali reviewed gene: DSG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12705872, 16439973, 16543896, 16575393, 17392831; Phenotypes: Hypotrichosis 6 - MIM#607903; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13991 DSPP Krithika Murali reviewed gene: DSPP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 39, with dentinogenesis - MIM#605594, Dentin dysplasia, type II - MIM#125420, Dentinogenesis imperfecta, Shields type II - MIM#125490, Dentinogenesis imperfecta, Shields type III - MIM#125500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13991 DUOX2 Krithika Murali reviewed gene: DUOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 6 - MIM#607200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13991 DUOXA2 Krithika Murali reviewed gene: DUOXA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 5 - MIM#274900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13991 LZTS1 Alison Yeung Gene: lzts1 has been classified as Red List (Low Evidence).
Mendeliome v0.13990 LZTS1 Alison Yeung Classified gene: LZTS1 as Red List (low evidence)
Mendeliome v0.13990 LZTS1 Alison Yeung Gene: lzts1 has been classified as Red List (Low Evidence).
Mendeliome v0.13989 LYZ Alison Yeung Gene: lyz has been classified as Green List (High Evidence).
Mendeliome v0.13989 LYZ Alison Yeung Phenotypes for gene: LYZ were changed from to Amyloidosis, renal, MIM# 105200
Mendeliome v0.13986 LYST Alison Yeung Gene: lyst has been classified as Green List (High Evidence).
Mendeliome v0.13984 LYRM7 Alison Yeung Gene: lyrm7 has been classified as Green List (High Evidence).
Mendeliome v0.13982 LYN Alison Yeung Gene: lyn has been classified as Red List (Low Evidence).
Mendeliome v0.13982 LYN Alison Yeung Classified gene: LYN as Red List (low evidence)
Mendeliome v0.13982 LYN Alison Yeung Gene: lyn has been classified as Red List (Low Evidence).
Mendeliome v0.13981 LTC4S Alison Yeung Gene: ltc4s has been classified as Red List (Low Evidence).
Mendeliome v0.13979 LTC4S Alison Yeung Classified gene: LTC4S as Red List (low evidence)
Mendeliome v0.13979 LTC4S Alison Yeung Gene: ltc4s has been classified as Red List (Low Evidence).
Mendeliome v0.13978 LTA Alison Yeung Gene: lta has been classified as Red List (Low Evidence).
Mendeliome v0.13976 LTA Alison Yeung Classified gene: LTA as Red List (low evidence)
Mendeliome v0.13976 LTA Alison Yeung Gene: lta has been classified as Red List (Low Evidence).
Mendeliome v0.13975 LRP6 Alison Yeung Gene: lrp6 has been classified as Green List (High Evidence).
Mendeliome v0.13975 LRP6 Alison Yeung Phenotypes for gene: LRP6 were changed from to Tooth agenesis, selective, 7, MIM# 616724
Mendeliome v0.13973 LRP5 Alison Yeung Gene: lrp5 has been classified as Green List (High Evidence).
Mendeliome v0.13973 LRP5 Alison Yeung Phenotypes for gene: LRP5 were changed from to Exudative vitreoretinopathy 4, MIM# 601813; Osteopetrosis, autosomal dominant 1, MIM# 607634; Osteoporosis-pseudoglioma syndrome, MIM# 259770; Osteosclerosis, MIM# 144750; Polycystic liver disease 4 with or without kidney cysts, MIM# 617875
Mendeliome v0.13971 LRP2 Alison Yeung Gene: lrp2 has been classified as Green List (High Evidence).
Mendeliome v0.13970 LRIG2 Alison Yeung Gene: lrig2 has been classified as Green List (High Evidence).
Mendeliome v0.13967 FGFR3 Bryony Thompson Gene: fgfr3 has been classified as Green List (High Evidence).
Mendeliome v0.13967 FGFR3 Bryony Thompson Phenotypes for gene: FGFR3 were changed from to achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833
Mendeliome v0.13964 FGFR3 Bryony Thompson reviewed gene: FGFR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26740388, 20301331, 20301540, 20301650, 20301628, 24864036, 17033969; Phenotypes: achondroplasia MONDO:0007037, Thanatophoric dysplasia type 1 MONDO:0008546, Thanatophoric dysplasia type 2 MONDO:0008547, hypochondroplasia MONDO:0007793, Muenke syndrome MONDO:0011274, FGFR3-related chondrodysplasia MONDO:0019685, severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658, camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504, Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13964 DNAJB6 Ain Roesley Gene: dnajb6 has been classified as Green List (High Evidence).
Mendeliome v0.13962 DNAH1 Ain Roesley Phenotypes for gene: DNAH1 were changed from Spermatogenic failure 18 MIM#617576 to primary ciliary dyskinesia,37 MIM#617577; Spermatogenic failure 18 MIM#617576
Mendeliome v0.13961 DNAH1 Ain Roesley Gene: dnah1 has been classified as Green List (High Evidence).
Mendeliome v0.13958 DNAH1 Ain Roesley reviewed gene: DNAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31507630, 31765523, 25927852, 24360805, 33577779; Phenotypes: primary ciliary dyskinesia,37 MIM#617577, Spermatogenic failure 18 MIM#617576; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13958 DNA2 Ain Roesley Gene: dna2 has been classified as Green List (High Evidence).
Mendeliome v0.13958 DNA2 Ain Roesley Phenotypes for gene: DNA2 were changed from to Seckel syndrome 8, MIM#615807; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 MIM#615156
Mendeliome v0.13956 DNA2 Ain Roesley reviewed gene: DNA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24389050, 31045292, 23352259, 25635128, 28554558; Phenotypes: Seckel syndrome 8, MIM#615807, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 MIM#615156; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13956 DMP1 Ain Roesley Gene: dmp1 has been classified as Green List (High Evidence).
Mendeliome v0.13954 AQP3 Elena Savva Gene: aqp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13954 DMD Ain Roesley Gene: dmd has been classified as Green List (High Evidence).
Mendeliome v0.13952 DLX3 Ain Roesley Gene: dlx3 has been classified as Green List (High Evidence).
Mendeliome v0.13952 DLX3 Ain Roesley Phenotypes for gene: DLX3 were changed from to Amelogenesis imperfecta, type IV, MIM# 104510; Trichodontoosseous syndrome, MIM# 190320
Mendeliome v0.13951 DLX3 Ain Roesley reviewed gene: DLX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9467018, 15666299, 18203197; Phenotypes: Amelogenesis imperfecta, type IV, MIM# 104510, Trichodontoosseous syndrome, MIM# 190320; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13951 DLAT Ain Roesley Gene: dlat has been classified as Green List (High Evidence).
Mendeliome v0.13949 DISC1 Ain Roesley Gene: disc1 has been classified as Red List (Low Evidence).
Mendeliome v0.13949 DISC1 Ain Roesley Classified gene: DISC1 as Red List (low evidence)
Mendeliome v0.13949 DISC1 Ain Roesley Gene: disc1 has been classified as Red List (Low Evidence).
Mendeliome v0.13948 LPL Alison Yeung Gene: lpl has been classified as Green List (High Evidence).
Mendeliome v0.13946 DHTKD1 Ain Roesley Gene: dhtkd1 has been classified as Green List (High Evidence).
Mendeliome v0.13943 LPAR6 Alison Yeung Gene: lpar6 has been classified as Green List (High Evidence).
Mendeliome v0.13943 LPAR6 Alison Yeung Phenotypes for gene: LPAR6 were changed from to Woolly hair, autosomal recessive 1, with or without hypotrichosis, MIM# 609239
Mendeliome v0.13941 LPAR6 Alison Yeung reviewed gene: LPAR6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Woolly hair, autosomal recessive 1, with or without hypotrichosis, MIM# 609239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13941 DHH Ain Roesley Gene: dhh has been classified as Green List (High Evidence).
Mendeliome v0.13941 DHH Ain Roesley Phenotypes for gene: DHH were changed from 46XY partial gonadal dysgenesis, with minifascicular neuropathy, MIM# 607080 to 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080; 46XY sex reversal 7 MIM#233420
Mendeliome v0.13940 LOXL1 Alison Yeung Gene: loxl1 has been classified as Red List (Low Evidence).
Mendeliome v0.13938 LOXL1 Alison Yeung Classified gene: LOXL1 as Red List (low evidence)
Mendeliome v0.13938 LOXL1 Alison Yeung Gene: loxl1 has been classified as Red List (Low Evidence).
Mendeliome v0.13937 LMF1 Alison Yeung Gene: lmf1 has been classified as Green List (High Evidence).
Mendeliome v0.13935 LMBRD1 Alison Yeung Gene: lmbrd1 has been classified as Green List (High Evidence).
Mendeliome v0.13932 LMBR1 Alison Yeung Gene: lmbr1 has been classified as Green List (High Evidence).
Mendeliome v0.13930 CYP27B1 Ain Roesley Gene: cyp27b1 has been classified as Green List (High Evidence).
Mendeliome v0.13928 CYP51A1 Ain Roesley Gene: cyp51a1 has been classified as Green List (High Evidence).
Mendeliome v0.13926 CYP4V2 Ain Roesley Gene: cyp4v2 has been classified as Green List (High Evidence).
Mendeliome v0.13924 CYP2R1 Ain Roesley Gene: cyp2r1 has been classified as Green List (High Evidence).
Mendeliome v0.13922 CYP2D6 Ain Roesley Gene: cyp2d6 has been classified as Red List (Low Evidence).
Mendeliome v0.13922 CYP2D6 Ain Roesley Phenotypes for gene: CYP2D6 were changed from to {Codeine sensitivity} MIM#608902; {Debrisoquine sensitivity} MIM#608902
Mendeliome v0.13921 CYP2D6 Ain Roesley Classified gene: CYP2D6 as Red List (low evidence)
Mendeliome v0.13921 CYP2D6 Ain Roesley Gene: cyp2d6 has been classified as Red List (Low Evidence).
Mendeliome v0.13920 CYP2D6 Ain Roesley reviewed gene: CYP2D6: Rating: RED; Mode of pathogenicity: None; Publications: 18406467, 24458010; Phenotypes: {Codeine sensitivity} MIM#608902, {Debrisoquine sensitivity} MIM#608902; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13920 CYP2C19 Ain Roesley Classified gene: CYP2C19 as Red List (low evidence)
Mendeliome v0.13920 CYP2C19 Ain Roesley Gene: cyp2c19 has been classified as Red List (Low Evidence).
Mendeliome v0.13919 CYP2C19 Ain Roesley changed review comment from: Voriconazole: Improved time to target concentration with genotype directed dosing (PMID 26616742), reduced underexposure (PMID: 31549389) (PMID 31549386)

(PMID:27981572)
Voriconazole, moderate strength.
Poor metabolizer: "Higher dose-adjusted trough concentrations of voriconazole and
may increase probability of adverse events."
Ultrarapid metabolizer: "probability of attainment of therapeutic voriconazole concentrations is small with standard dosing."; to: Pharmacogenomics gene

Voriconazole: Improved time to target concentration with genotype directed dosing (PMID 26616742), reduced underexposure (PMID: 31549389) (PMID 31549386)

(PMID:27981572)
Voriconazole, moderate strength.
Poor metabolizer: "Higher dose-adjusted trough concentrations of voriconazole and
may increase probability of adverse events."
Ultrarapid metabolizer: "probability of attainment of therapeutic voriconazole concentrations is small with standard dosing."
Mendeliome v0.13919 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Mendeliome v0.13919 DGUOK Zornitza Stark Phenotypes for gene: DGUOK were changed from to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880; Portal hypertension, noncirrhotic, 1, MIM# 617068; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, MIM# 617070
Mendeliome v0.13916 DGUOK Zornitza Stark reviewed gene: DGUOK: Rating: GREEN; Mode of pathogenicity: None; Publications: 11687800, 12874104, 15887277, 23043144, 26874653; Phenotypes: Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880, Portal hypertension, noncirrhotic, 1, MIM# 617068, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, MIM# 617070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13916 DGKE Zornitza Stark Gene: dgke has been classified as Green List (High Evidence).
Mendeliome v0.13913 DES Zornitza Stark Gene: des has been classified as Green List (High Evidence).
Mendeliome v0.13911 DEPDC5 Zornitza Stark Gene: depdc5 has been classified as Green List (High Evidence).
Mendeliome v0.13908 DECR1 Zornitza Stark Gene: decr1 has been classified as Red List (Low Evidence).
Mendeliome v0.13908 DECR1 Zornitza Stark Classified gene: DECR1 as Red List (low evidence)
Mendeliome v0.13908 DECR1 Zornitza Stark Gene: decr1 has been classified as Red List (Low Evidence).
Mendeliome v0.13907 DDIT3 Zornitza Stark Gene: ddit3 has been classified as Red List (Low Evidence).
Mendeliome v0.13907 DDIT3 Zornitza Stark Classified gene: DDIT3 as Red List (low evidence)
Mendeliome v0.13907 DDIT3 Zornitza Stark Gene: ddit3 has been classified as Red List (Low Evidence).
Mendeliome v0.13906 DDHD2 Zornitza Stark Gene: ddhd2 has been classified as Green List (High Evidence).
Mendeliome v0.13906 DDHD2 Zornitza Stark Phenotypes for gene: DDHD2 were changed from to Spastic paraplegia 54, autosomal recessive, MIM# 615033
Mendeliome v0.13903 DDHD2 Zornitza Stark reviewed gene: DDHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23486545, 24482476, 23176823, 31302745; Phenotypes: Spastic paraplegia 54, autosomal recessive, MIM# 615033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13903 DDC Zornitza Stark Gene: ddc has been classified as Green List (High Evidence).
Mendeliome v0.13900 DDB2 Zornitza Stark Gene: ddb2 has been classified as Green List (High Evidence).
Mendeliome v0.13897 AQP3 Elena Savva Classified gene: AQP3 as Amber List (moderate evidence)
Mendeliome v0.13897 AQP3 Elena Savva Gene: aqp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13895 DCTN1 Zornitza Stark Gene: dctn1 has been classified as Green List (High Evidence).
Mendeliome v0.13891 AQP5 Elena Savva Gene: aqp5 has been classified as Green List (High Evidence).
Mendeliome v0.13890 AR Elena Savva Phenotypes for gene: AR were changed from to Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300; Spinal and bulbar muscular atrophy of Kennedy MIM#313200
Mendeliome v0.13888 AR Elena Savva reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22334387; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300, Spinal and bulbar muscular atrophy of Kennedy MIM#313200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.13888 DCLRE1C Zornitza Stark Gene: dclre1c has been classified as Green List (High Evidence).
Mendeliome v0.13885 ARCN1 Elena Savva Gene: arcn1 has been classified as Green List (High Evidence).
Mendeliome v0.13884 DCHS1 Zornitza Stark Gene: dchs1 has been classified as Green List (High Evidence).
Mendeliome v0.13881 APPL1 Elena Savva Classified gene: APPL1 as Amber List (moderate evidence)
Mendeliome v0.13881 APPL1 Elena Savva Gene: appl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13880 APPL1 Elena Savva Classified gene: APPL1 as Amber List (moderate evidence)
Mendeliome v0.13880 APPL1 Elena Savva Gene: appl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13879 APPL1 Elena Savva Gene: appl1 has been classified as Green List (High Evidence).
Mendeliome v0.13879 AQP1 Elena Savva Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension
Mendeliome v0.13878 APRT Elena Savva Gene: aprt has been classified as Green List (High Evidence).
Mendeliome v0.13878 AQP1 Elena Savva Phenotypes for gene: AQP1 were changed from to Pulmonary arterial hypertension
Mendeliome v0.13877 AQP1 Elena Savva Gene: aqp1 has been classified as Green List (High Evidence).
Mendeliome v0.13875 AQP1 Elena Savva reviewed gene: AQP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:22683574, 29650961; Phenotypes: Pulmonary arterial hypertension; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Gene: apoc4-apoc2 has been classified as Red List (Low Evidence).
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Classified gene: APOC4-APOC2 as Red List (low evidence)
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Gene: apoc4-apoc2 has been classified as Red List (Low Evidence).
Mendeliome v0.13870 APOC2 Elena Savva Gene: apoc2 has been classified as Green List (High Evidence).
Mendeliome v0.13868 APOC3 Elena Savva Gene: apoc3 has been classified as Red List (Low Evidence).
Mendeliome v0.13866 APOC3 Elena Savva Classified gene: APOC3 as Red List (low evidence)
Mendeliome v0.13866 APOC3 Elena Savva Gene: apoc3 has been classified as Red List (Low Evidence).
Mendeliome v0.13863 CCDC50 Zornitza Stark Classified gene: CCDC50 as Amber List (moderate evidence)
Mendeliome v0.13863 CCDC50 Zornitza Stark Gene: ccdc50 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13860 DCAF17 Zornitza Stark Gene: dcaf17 has been classified as Green List (High Evidence).
Mendeliome v0.13857 CYP2C19 Ain Roesley Gene: cyp2c19 has been classified as Green List (High Evidence).
Mendeliome v0.13856 CYP2B6 Ain Roesley Gene: cyp2b6 has been classified as Red List (Low Evidence).
Mendeliome v0.13855 CYP2B6 Ain Roesley Classified gene: CYP2B6 as Red List (low evidence)
Mendeliome v0.13855 CYP2B6 Ain Roesley Gene: cyp2b6 has been classified as Red List (Low Evidence).
Mendeliome v0.13854 DAZ4 Zornitza Stark Gene: daz4 has been classified as Red List (Low Evidence).
Mendeliome v0.13854 DAZ4 Zornitza Stark Classified gene: DAZ4 as Red List (low evidence)
Mendeliome v0.13854 DAZ4 Zornitza Stark Gene: daz4 has been classified as Red List (Low Evidence).
Mendeliome v0.13853 DAZ3 Zornitza Stark Gene: daz3 has been classified as Red List (Low Evidence).
Mendeliome v0.13853 DAZ3 Zornitza Stark Classified gene: DAZ3 as Red List (low evidence)
Mendeliome v0.13853 DAZ3 Zornitza Stark Gene: daz3 has been classified as Red List (Low Evidence).
Mendeliome v0.13852 CYP2A6 Ain Roesley Gene: cyp2a6 has been classified as Red List (Low Evidence).
Mendeliome v0.13852 CYP2A6 Ain Roesley Phenotypes for gene: CYP2A6 were changed from to Coumarin resistance MIM#122700
Mendeliome v0.13852 CYP2A6 Ain Roesley Classified gene: CYP2A6 as Red List (low evidence)
Mendeliome v0.13852 CYP2A6 Ain Roesley Gene: cyp2a6 has been classified as Red List (Low Evidence).
Mendeliome v0.13851 CYP2A6 Ain Roesley reviewed gene: CYP2A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coumarin resistance MIM#122700; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13851 DAZ2 Zornitza Stark Gene: daz2 has been classified as Red List (Low Evidence).
Mendeliome v0.13851 DAZ2 Zornitza Stark Classified gene: DAZ2 as Red List (low evidence)
Mendeliome v0.13851 DAZ2 Zornitza Stark Gene: daz2 has been classified as Red List (Low Evidence).
Mendeliome v0.13850 DAZ1 Zornitza Stark Gene: daz1 has been classified as Red List (Low Evidence).
Mendeliome v0.13850 DAZ1 Zornitza Stark Classified gene: DAZ1 as Red List (low evidence)
Mendeliome v0.13850 DAZ1 Zornitza Stark Gene: daz1 has been classified as Red List (Low Evidence).
Mendeliome v0.13849 CYP27A1 Ain Roesley Phenotypes for gene: CYP27A1 were changed from Cerebrotendinous xanthomatosis MIM#213700; Disorders of bile acid biosynthesis to Cerebrotendinous xanthomatosis MIM#213700; Disorders of bile acid biosynthesis
Mendeliome v0.13848 CYP27A1 Ain Roesley Gene: cyp27a1 has been classified as Green List (High Evidence).
Mendeliome v0.13848 CYP27A1 Ain Roesley Phenotypes for gene: CYP27A1 were changed from to Cerebrotendinous xanthomatosis MIM#213700; Disorders of bile acid biosynthesis
Mendeliome v0.13846 DARS2 Zornitza Stark Gene: dars2 has been classified as Green List (High Evidence).
Mendeliome v0.13845 CYP26C1 Ain Roesley Gene: cyp26c1 has been classified as Green List (High Evidence).
Mendeliome v0.13845 CYP26C1 Ain Roesley Phenotypes for gene: CYP26C1 were changed from to Focal facial dermal dysplasia 4 MIM#614974
Mendeliome v0.13843 DARS2 Zornitza Stark changed review comment from: Slowly progressive disorder with variable age of onset, multiple families reported.; to: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy (Scheper et al., 2007). Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline.
Mendeliome v0.13842 CYP26C1 Ain Roesley reviewed gene: CYP26C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29263414, 23161670, 16530710; Phenotypes: Focal facial dermal dysplasia 4 MIM#614974; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13842 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Mendeliome v0.13839 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Mendeliome v0.13839 CYP7B1 Zornitza Stark Phenotypes for gene: CYP7B1 were changed from to Bile acid synthesis defect, congenital, 3 MIM#613812; Spastic paraplegia 5A, autosomal recessive MIM#270800; Disorders of bile acid biosynthesis
Mendeliome v0.13836 CYP1A2 Ain Roesley Gene: cyp1a2 has been classified as Red List (Low Evidence).
Mendeliome v0.13836 CYP1A2 Ain Roesley Classified gene: CYP1A2 as Red List (low evidence)
Mendeliome v0.13836 CYP1A2 Ain Roesley Gene: cyp1a2 has been classified as Red List (Low Evidence).
Mendeliome v0.13835 KLF4 Zornitza Stark Gene: klf4 has been classified as Green List (High Evidence).
Mendeliome v0.13834 CYP19A1 Ain Roesley Gene: cyp19a1 has been classified as Green List (High Evidence).
Mendeliome v0.13832 CYCS Ain Roesley Gene: cycs has been classified as Green List (High Evidence).
Mendeliome v0.13829 NRG1 Zornitza Stark Classified gene: NRG1 as Amber List (moderate evidence)
Mendeliome v0.13829 NRG1 Zornitza Stark Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13828 CYC1 Ain Roesley Gene: cyc1 has been classified as Green List (High Evidence).
Mendeliome v0.13825 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 to oculopharyngeal muscular dystrophy, MONDO:0008116; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422
Mendeliome v0.13824 HNRNPA2B1 Zornitza Stark Classified gene: HNRNPA2B1 as Green List (high evidence)
Mendeliome v0.13824 HNRNPA2B1 Zornitza Stark Gene: hnrnpa2b1 has been classified as Green List (High Evidence).
Mendeliome v0.13823 DTYMK Zornitza Stark Phenotypes for gene: DTYMK were changed from Intellectual disability; microcephaly to Neurodegeneration, childhood-onset, with progressive microcephaly (MIM# 619847)
Mendeliome v0.13821 DTYMK Zornitza Stark Classified gene: DTYMK as Green List (high evidence)
Mendeliome v0.13821 DTYMK Zornitza Stark Gene: dtymk has been classified as Green List (High Evidence).
Mendeliome v0.13820 KCNH5 Zornitza Stark Gene: kcnh5 has been classified as Green List (High Evidence).
Mendeliome v0.13820 CREB1 Zornitza Stark Phenotypes for gene: CREB1 were changed from corpus callosum agenesis; thyroid follicular hypoplasia to Agenesis of corpus callosum, MONDO:0009022
Mendeliome v0.13819 CREB1 Zornitza Stark reviewed gene: CREB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Agenesis of corpus callosum, MONDO:0009022; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13819 SLC16A12 Zornitza Stark Gene: slc16a12 has been classified as Green List (High Evidence).
Mendeliome v0.13816 SLC14A1 Zornitza Stark Gene: slc14a1 has been classified as Red List (Low Evidence).
Mendeliome v0.13813 SLC14A1 Zornitza Stark Classified gene: SLC14A1 as Red List (low evidence)
Mendeliome v0.13813 SLC14A1 Zornitza Stark Gene: slc14a1 has been classified as Red List (Low Evidence).
Mendeliome v0.13812 SLC12A5 Zornitza Stark Gene: slc12a5 has been classified as Green List (High Evidence).
Mendeliome v0.13809 CORIN Zornitza Stark Gene: corin has been classified as Red List (Low Evidence).
Mendeliome v0.13809 DUSP6 Zornitza Stark Gene: dusp6 has been classified as Red List (Low Evidence).
Mendeliome v0.13806 DUSP6 Zornitza Stark Classified gene: DUSP6 as Red List (low evidence)
Mendeliome v0.13806 DUSP6 Zornitza Stark Gene: dusp6 has been classified as Red List (Low Evidence).
Mendeliome v0.13805 DYRK1B Zornitza Stark Gene: dyrk1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13805 DYRK1B Zornitza Stark Phenotypes for gene: DYRK1B were changed from to Abdominal obesity-metabolic syndrome 3 - MIM#615812
Mendeliome v0.13802 DYRK1B Zornitza Stark Classified gene: DYRK1B as Amber List (moderate evidence)
Mendeliome v0.13802 DYRK1B Zornitza Stark Gene: dyrk1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13800 KLF4 Elena Savva Classified gene: KLF4 as Green List (high evidence)
Mendeliome v0.13800 KLF4 Elena Savva Gene: klf4 has been classified as Green List (High Evidence).
Mendeliome v0.13799 DTYMK Daniel Flanagan reviewed gene: DTYMK: Rating: GREEN; Mode of pathogenicity: None; Publications: 34918187, 31271740; Phenotypes: Neurodegeneration, childhood-onset, with progressive microcephaly (MIM# 619847); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13799 NRG1 Alison Yeung Classified gene: NRG1 as Red List (low evidence)
Mendeliome v0.13799 NRG1 Alison Yeung Added comment: Comment on list classification: Red for peripheral neuropathy (single family reported)
Amber for Hirschsprung disease
Mendeliome v0.13799 NRG1 Alison Yeung Gene: nrg1 has been classified as Red List (Low Evidence).
Mendeliome v0.13798 KLF4 Elena Savva gene: KLF4 was added
gene: KLF4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KLF4 were set to PMID: 35168889; 10431239
Phenotypes for gene: KLF4 were set to Hereditary palmoplantar keratoderma MONDO:0019272, KFL4-related
Review for gene: KLF4 was set to GREEN
Added comment: PMID: 35168889 - 3 patients from 2 unrelated families with palmoplantar keratoderma. Two variants found, fs and a missense.
Functional studies on patient skin biopsy shows "slightly but significantly decreased" protein expression in both children.
Gene was shown to bind the DSG1 promoter and regulate expression. Transfected cells showed reduced DSG1 expression.

PMID: 10431239 - mouse K/O died shortly after birth due to loss of skin barrier function

gnomAD: single het fs in the population
Sources: Literature
Mendeliome v0.13797 CTR9 Zornitza Stark Gene: ctr9 has been classified as Green List (High Evidence).
Mendeliome v0.13797 CTR9 Zornitza Stark Classified gene: CTR9 as Green List (high evidence)
Mendeliome v0.13797 CTR9 Zornitza Stark Gene: ctr9 has been classified as Green List (High Evidence).
Mendeliome v0.13796 CDH4 Ain Roesley Gene: cdh4 has been classified as Red List (Low Evidence).
Mendeliome v0.13796 DNAH14 Zornitza Stark Gene: dnah14 has been classified as Green List (High Evidence).
Mendeliome v0.13796 DNAH14 Zornitza Stark Classified gene: DNAH14 as Green List (high evidence)
Mendeliome v0.13796 DNAH14 Zornitza Stark Gene: dnah14 has been classified as Green List (High Evidence).
Mendeliome v0.13793 CD164 Alison Yeung Gene: cd164 has been classified as Green List (High Evidence).
Mendeliome v0.13793 CD164 Alison Yeung Classified gene: CD164 as Green List (high evidence)
Mendeliome v0.13793 CD164 Alison Yeung Gene: cd164 has been classified as Green List (High Evidence).
Mendeliome v0.13791 TULP3 Zornitza Stark Gene: tulp3 has been classified as Green List (High Evidence).
Mendeliome v0.13791 TULP3 Zornitza Stark Classified gene: TULP3 as Green List (high evidence)
Mendeliome v0.13791 TULP3 Zornitza Stark Gene: tulp3 has been classified as Green List (High Evidence).
Mendeliome v0.13791 BMPR1B Ain Roesley Phenotypes for gene: BMPR1B were changed from Acromesomelic dysplasia, Demirhan type, MIM# 609441; Brachydactyly, type A1, D, MIM# 616849; Brachydactyly, type A2, MIM# 112600 to Acromesomelic dysplasia, Demirhan type, MIM# 609441; Brachydactyly, type A1, D, MIM# 616849; Brachydactyly, type A2, MIM# 112600; coloboma MONDO#0001476, BMPR1B-related
Mendeliome v0.13789 ANK3 Ain Roesley Phenotypes for gene: ANK3 were changed from Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related to Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related
Mendeliome v0.13788 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770 to Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770
Mendeliome v0.13788 ANK3 Ain Roesley Phenotypes for gene: ANK3 were changed from Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant to Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related
Mendeliome v0.13789 KCNH5 Elena Savva Classified gene: KCNH5 as Green List (high evidence)
Mendeliome v0.13789 KCNH5 Elena Savva Gene: kcnh5 has been classified as Green List (High Evidence).
Mendeliome v0.13787 TULP3 Anna Ritchie gene: TULP3 was added
gene: TULP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to PMID: 35397207
Phenotypes for gene: TULP3 were set to progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045
Review for gene: TULP3 was set to GREEN
Added comment: 15 individuals from eight unrelated families with bi-allelic variants in TULP3 were detected. The affected individuals reported are mostly adults, in the 3rd through 7th decades of life, and presented with progressive degenerative liver fibrosis with variable fibrocystic kidney disease and hypertrophic cardiomyopathy.

The human phenotype was ecapitulated in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals
Sources: Literature
Mendeliome v0.13786 DROSHA Zornitza Stark Gene: drosha has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13786 DROSHA Zornitza Stark Classified gene: DROSHA as Amber List (moderate evidence)
Mendeliome v0.13786 DROSHA Zornitza Stark Gene: drosha has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13786 KCNH5 Elena Savva Classified gene: KCNH5 as Green List (high evidence)
Mendeliome v0.13786 KCNH5 Elena Savva Gene: kcnh5 has been classified as Green List (High Evidence).
Mendeliome v0.13784 PRDM13 Dean Phelan reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35390279; Phenotypes: Pontocerebellar hypoplasia (MONDO:0020135), PRDM13 related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13784 DROSHA Lucy Spencer gene: DROSHA was added
gene: DROSHA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DROSHA were set to 35405010
Phenotypes for gene: DROSHA were set to Neurodevelopmental disorder (MONDO#0700092), DROSHA-related
Review for gene: DROSHA was set to AMBER
Added comment: 2 individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly, and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. Both variants are missense, absent from gnomad. Both individuals noted to have Rett-like features.

Functional studies in patient fibroblasts showed one of the missense altered the expression of mature miRNA. Fruit fly models with homozygous LOF variants die during larval stages. introduction of the missense seen in the patients was able to partially rescue this phenotype suggesting LOF is not the mechanism.
Sources: Literature
Mendeliome v0.13783 PPFIBP1 Zornitza Stark Gene: ppfibp1 has been classified as Green List (High Evidence).
Mendeliome v0.13783 STX1A Ain Roesley Gene: stx1a has been classified as Green List (High Evidence).
Mendeliome v0.13782 STX1A Ain Roesley changed review comment from: Preprint:
8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown)

7 unrelated since the 2 siblings share similar features:
7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria
Sources: Literature; to: Preprint: https://www.medrxiv.org/content/10.1101/2022.04.20.22274073v1
8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown)

7 unrelated since the 2 siblings share similar features:
7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria
Sources: Literature
Mendeliome v0.13782 PPFIBP1 Zornitza Stark Classified gene: PPFIBP1 as Green List (high evidence)
Mendeliome v0.13782 PPFIBP1 Zornitza Stark Gene: ppfibp1 has been classified as Green List (High Evidence).
Mendeliome v0.13781 PPFIBP1 Zornitza Stark gene: PPFIBP1 was added
gene: PPFIBP1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: PPFIBP1 was set to GREEN
Added comment: 16 individuals from 10 unrelated families reported with moderate to profound developmental delay, often refractory early-onset epilepsy and progressive microcephaly. Drosophila model.
Sources: Expert Review
Mendeliome v0.13779 STX1A Ain Roesley Classified gene: STX1A as Green List (high evidence)
Mendeliome v0.13779 STX1A Ain Roesley Gene: stx1a has been classified as Green List (High Evidence).
Mendeliome v0.13778 STX1A Ain Roesley gene: STX1A was added
gene: STX1A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: STX1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Review for gene: STX1A was set to GREEN
gene: STX1A was marked as current diagnostic
Added comment: Preprint:
8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown)

7 unrelated since the 2 siblings share similar features:
7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria
Sources: Literature
Mendeliome v0.13777 HYDIN Zornitza Stark Gene: hydin has been classified as Green List (High Evidence).
Mendeliome v0.13777 HYDIN Zornitza Stark Phenotypes for gene: HYDIN were changed from to Ciliary dyskinesia, primary, 5 (MIM#608647)
Mendeliome v0.13774 HYDIN Zornitza Stark reviewed gene: HYDIN: Rating: GREEN; Mode of pathogenicity: None; Publications: 23022101, 23849777, 28441829, 31116566; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#608647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13774 HTRA2 Zornitza Stark Gene: htra2 has been classified as Green List (High Evidence).
Mendeliome v0.13771 HTR1A Zornitza Stark Gene: htr1a has been classified as Red List (Low Evidence).
Mendeliome v0.13768 HTR1A Zornitza Stark Classified gene: HTR1A as Red List (low evidence)
Mendeliome v0.13768 HTR1A Zornitza Stark Gene: htr1a has been classified as Red List (Low Evidence).
Mendeliome v0.13767 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Green List (High Evidence).
Mendeliome v0.13764 HSD3B7 Zornitza Stark Gene: hsd3b7 has been classified as Green List (High Evidence).
Mendeliome v0.13764 HSD3B7 Zornitza Stark Phenotypes for gene: HSD3B7 were changed from to Bile acid synthesis defect, congenital, 1 MIM#607765; Disorders of bile acid biosynthesis
Mendeliome v0.13761 HSD3B2 Zornitza Stark Gene: hsd3b2 has been classified as Green List (High Evidence).
Mendeliome v0.13761 HSD3B2 Zornitza Stark Phenotypes for gene: HSD3B2 were changed from to Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency, MIM# 201810
Mendeliome v0.13758 HSD3B2 Zornitza Stark reviewed gene: HSD3B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1363812, 18252794; Phenotypes: Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency, MIM# 201810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13758 CUBN Ain Roesley Gene: cubn has been classified as Green List (High Evidence).
Mendeliome v0.13755 CTSF Ain Roesley Gene: ctsf has been classified as Green List (High Evidence).
Mendeliome v0.13755 CTSF Ain Roesley Phenotypes for gene: CTSF were changed from to Ceroid lipofuscinosis, neuronal, 13, Kufs type, MIM# 615362
Mendeliome v0.13753 CTSF Ain Roesley reviewed gene: CTSF: Rating: GREEN; Mode of pathogenicity: None; Publications: 28749476, 27668283, 27524508; Phenotypes: Ceroid lipofuscinosis, neuronal, 13, Kufs type, MIM# 615362; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13753 CTSC Ain Roesley Gene: ctsc has been classified as Green List (High Evidence).
Mendeliome v0.13750 CTNS Ain Roesley Gene: ctns has been classified as Green List (High Evidence).
Mendeliome v0.13750 CTNS Ain Roesley Phenotypes for gene: CTNS were changed from to Cystinosis, atypical nephropathic MIM#219800; Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900; Cystinosis, nephropathic MIM#219800; Cystinosis, ocular nonnephropathic MIM#219750
Mendeliome v0.13747 CTNS Ain Roesley reviewed gene: CTNS: Rating: ; Mode of pathogenicity: None; Publications: 20301574, 9537412, 31068690; Phenotypes: Cystinosis, atypical nephropathic MIM#219800, Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900, Cystinosis, nephropathic MIM#219800, Cystinosis, ocular nonnephropathic MIM#219750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13747 CTNNA1 Ain Roesley Gene: ctnna1 has been classified as Green List (High Evidence).
Mendeliome v0.13745 CTHRC1 Ain Roesley Gene: cthrc1 has been classified as Red List (Low Evidence).
Mendeliome v0.13744 CTHRC1 Ain Roesley Classified gene: CTHRC1 as Red List (low evidence)
Mendeliome v0.13744 CTHRC1 Ain Roesley Gene: cthrc1 has been classified as Red List (Low Evidence).
Mendeliome v0.13743 CSRP3 Ain Roesley Gene: csrp3 has been classified as Green List (High Evidence).
Mendeliome v0.13741 CRYGS Ain Roesley Gene: crygs has been classified as Green List (High Evidence).
Mendeliome v0.13739 CRYGB Ain Roesley Gene: crygb has been classified as Red List (Low Evidence).
Mendeliome v0.13738 CRYGB Ain Roesley Classified gene: CRYGB as Red List (low evidence)
Mendeliome v0.13738 CRYGB Ain Roesley Gene: crygb has been classified as Red List (Low Evidence).
Mendeliome v0.13737 CRYAB Ain Roesley Gene: cryab has been classified as Green List (High Evidence).
Mendeliome v0.13735 CRX Ain Roesley Gene: crx has been classified as Green List (High Evidence).
Mendeliome v0.13735 CRX Ain Roesley Phenotypes for gene: CRX were changed from to Leber congenital amaurosis 7, MIM# 613829; Cone-rod retinal dystrophy-2 MIM#120970
Mendeliome v0.13733 CRX Ain Roesley reviewed gene: CRX: Rating: GREEN; Mode of pathogenicity: None; Publications: 12208271, 9931337, 9537410, 29568065, 27427859, 25270190, 32927963, 33910785; Phenotypes: Leber congenital amaurosis 7, MIM# 613829, Cone-rod retinal dystrophy-2 MIM#120970; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13733 CREB1 Ain Roesley Classified gene: CREB1 as Red List (low evidence)
Mendeliome v0.13733 CREB1 Ain Roesley Gene: creb1 has been classified as Red List (Low Evidence).
Mendeliome v0.13732 CREB1 Ain Roesley Gene: creb1 has been classified as Green List (High Evidence).
Mendeliome v0.13732 CREB1 Ain Roesley Phenotypes for gene: CREB1 were changed from to corpus callosum agenesis; thyroid follicular hypoplasia
Mendeliome v0.13729 CREB1 Ain Roesley reviewed gene: CREB1: Rating: RED; Mode of pathogenicity: None; Publications: 22267179; Phenotypes: corpus callosum agenesis, thyroid follicular hypoplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13729 CRBN Ain Roesley Gene: crbn has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13729 CRBN Ain Roesley Phenotypes for gene: CRBN were changed from to Intellectual developmental disorder, autosomal recessive 2 MIM#607417
Mendeliome v0.13728 CRBN Ain Roesley Classified gene: CRBN as Amber List (moderate evidence)
Mendeliome v0.13728 CRBN Ain Roesley Gene: crbn has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13727 CRBN Ain Roesley reviewed gene: CRBN: Rating: AMBER; Mode of pathogenicity: None; Publications: 15557513, 28143899; Phenotypes: Intellectual developmental disorder, autosomal recessive 2 MIM#607417; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13727 CRB1 Ain Roesley Gene: crb1 has been classified as Green List (High Evidence).
Mendeliome v0.13727 CRB1 Ain Roesley Phenotypes for gene: CRB1 were changed from to Leber congenital amaurosis 8 MIM#613835; Pigmented paravenous chorioretinal atrophy MIM#172870; Retinitis pigmentosa-12 MIM#600105
Mendeliome v0.13725 CRB1 Ain Roesley reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30285347, 32922261, 31884620, 15459956; Phenotypes: Leber congenital amaurosis 8 MIM#613835, Pigmented paravenous chorioretinal atrophy MIM#172870, Retinitis pigmentosa-12 MIM#600105; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13725 CPT1A Ain Roesley Gene: cpt1a has been classified as Green List (High Evidence).
Mendeliome v0.13723 CPS1 Ain Roesley Gene: cps1 has been classified as Green List (High Evidence).
Mendeliome v0.13722 CPOX Ain Roesley Gene: cpox has been classified as Green List (High Evidence).
Mendeliome v0.13720 CPN1 Ain Roesley Gene: cpn1 has been classified as Red List (Low Evidence).
Mendeliome v0.13718 CPN1 Ain Roesley Classified gene: CPN1 as Red List (low evidence)
Mendeliome v0.13718 CPN1 Ain Roesley Gene: cpn1 has been classified as Red List (Low Evidence).
Mendeliome v0.13717 COMP Ain Roesley Gene: comp has been classified as Green List (High Evidence).
Mendeliome v0.13717 HSD11B1 Zornitza Stark Gene: hsd11b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13714 HSD11B1 Zornitza Stark Classified gene: HSD11B1 as Amber List (moderate evidence)
Mendeliome v0.13714 HSD11B1 Zornitza Stark Gene: hsd11b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13713 HRG Zornitza Stark Gene: hrg has been classified as Green List (High Evidence).
Mendeliome v0.13710 HP Zornitza Stark Gene: hp has been classified as Red List (Low Evidence).
Mendeliome v0.13709 HP Zornitza Stark Classified gene: HP as Red List (low evidence)
Mendeliome v0.13709 HP Zornitza Stark Gene: hp has been classified as Red List (Low Evidence).
Mendeliome v0.13708 HOXD13 Zornitza Stark Gene: hoxd13 has been classified as Green List (High Evidence).
Mendeliome v0.13705 HOXA13 Zornitza Stark Gene: hoxa13 has been classified as Green List (High Evidence).
Mendeliome v0.13702 HOXA1 Zornitza Stark Gene: hoxa1 has been classified as Green List (High Evidence).
Mendeliome v0.13702 HOXA1 Zornitza Stark Phenotypes for gene: HOXA1 were changed from to Athabaskan brainstem dysgenesis syndrome MIM#601536; Bosley-Salih-Alorainy syndrome MIM#601536
Mendeliome v0.13699 HOXA1 Zornitza Stark reviewed gene: HOXA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16155570, 18412118, 32864817; Phenotypes: Athabaskan brainstem dysgenesis syndrome MIM#601536, Bosley-Salih-Alorainy syndrome MIM#601536; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13699 HNRNPA1 Zornitza Stark Gene: hnrnpa1 has been classified as Green List (High Evidence).
Mendeliome v0.13699 HNRNPA1 Zornitza Stark Phenotypes for gene: HNRNPA1 were changed from to Amyotrophic lateral sclerosis 20 MIM#615426
Mendeliome v0.13696 HNRNPA1 Zornitza Stark reviewed gene: HNRNPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23455423, 34291734; Phenotypes: Amyotrophic lateral sclerosis 20 MIM#615426; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13696 HNF4A Zornitza Stark Gene: hnf4a has been classified as Green List (High Evidence).
Mendeliome v0.13693 HNF1A Zornitza Stark Gene: hnf1a has been classified as Green List (High Evidence).
Mendeliome v0.13690 HMX1 Zornitza Stark Gene: hmx1 has been classified as Green List (High Evidence).
Mendeliome v0.13687 HMX1 Zornitza Stark changed review comment from: Oculoauricular syndrome (OCACS) is characterized by complex ocular anomalies, including congenital cataract, anterior segment dysgenesis, iris coloboma, and early-onset retinal dystrophy, and dysplastic ears with abnormal external ear cartilage.

At least two families and two animal models. Also evidence that duplication of long-range enhancer causes microbial.; to: Oculoauricular syndrome (OCACS) is characterized by complex ocular anomalies, including congenital cataract, anterior segment dysgenesis, iris coloboma, and early-onset retinal dystrophy, and dysplastic ears with abnormal external ear cartilage.

At least two families and two animal models. Also evidence that duplication of long-range enhancer causes microtia.
Mendeliome v0.13687 COL9A1 Ain Roesley Gene: col9a1 has been classified as Green List (High Evidence).
Mendeliome v0.13685 CORIN Ain Roesley Phenotypes for gene: CORIN were changed from to Preeclampsia/eclampsia 5 MIM#614595
Mendeliome v0.13684 CORIN Ain Roesley Classified gene: CORIN as Red List (low evidence)
Mendeliome v0.13684 CORIN Ain Roesley Added comment: Comment on list classification: pre-eclampsia is typically not monogenic
Mendeliome v0.13684 CORIN Ain Roesley Gene: corin has been classified as Red List (Low Evidence).
Mendeliome v0.13683 CORIN Ain Roesley reviewed gene: CORIN: Rating: AMBER; Mode of pathogenicity: None; Publications: 22437503; Phenotypes: Preeclampsia/eclampsia 5 MIM#614595; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13683 DUSP6 Krithika Murali changed review comment from: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing.

Summary of DUSP6 variants identified in this study
c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3
c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual
c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant)
c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant

No segregation information provided.

PMID: 23643382 - Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism. In 5 unrelated individuals with congenital hypogonadotropic hypogonadism 4 heterozygous missense were identified. In 3 of the probands, the DUSP6 mutation was accompanied by a heterozygous missense mutation in another HH-associated gene. 3 of the 4 variants have subpopulation allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Thr346Met (AJ AF 0.002797), p.Ser182Phe (NFE AF 0.001396), p.Asn189Ser (NFE AF 0.0003641). No functional assays were conducted.

PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted.; to: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing.

Summary of DUSP6 variants identified in this study
c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3
c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual
c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant)
c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant

No segregation information provided. Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism.

PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted.
Mendeliome v0.13683 DUSP6 Krithika Murali changed review comment from: 1 study cited by OMIM (Miraoui et al 2013) - heterozygous variants in 5 unrelated individuals with congenital hypogonadotrophic hypogonadism (CHH). 4/5 variants highly prevalent in healthy population and/or in conjunction with variants in other genes either known to be associated with CHH or possibly associated. No additional studies published since this paper.

PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing.

Summary of DUSP6 variants identified in this study
c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3
c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual
c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant)
c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant

No segregation information provided.; to: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing.

Summary of DUSP6 variants identified in this study
c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3
c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual
c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant)
c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant

No segregation information provided.

PMID: 23643382 - Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism. In 5 unrelated individuals with congenital hypogonadotropic hypogonadism 4 heterozygous missense were identified. In 3 of the probands, the DUSP6 mutation was accompanied by a heterozygous missense mutation in another HH-associated gene. 3 of the 4 variants have subpopulation allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Thr346Met (AJ AF 0.002797), p.Ser182Phe (NFE AF 0.001396), p.Asn189Ser (NFE AF 0.0003641). No functional assays were conducted.

PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted.
Mendeliome v0.13683 COQ9 Ain Roesley Gene: coq9 has been classified as Green List (High Evidence).
Mendeliome v0.13681 COQ8B Ain Roesley Gene: coq8b has been classified as Green List (High Evidence).
Mendeliome v0.13680 COQ8A Ain Roesley Gene: coq8a has been classified as Green List (High Evidence).
Mendeliome v0.13679 COQ7 Ain Roesley Gene: coq7 has been classified as Green List (High Evidence).
Mendeliome v0.13678 COQ6 Ain Roesley Gene: coq6 has been classified as Green List (High Evidence).
Mendeliome v0.13676 COMP Ain Roesley Phenotypes for gene: COMP were changed from to Epiphyseal dysplasia, multiple, 1 MIM#132400; Pseudoachondroplasia MIM#177170
Mendeliome v0.13675 COMP Ain Roesley reviewed gene: COMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301302, 20301660; Phenotypes: Epiphyseal dysplasia, multiple, 1 MIM#132400, Pseudoachondroplasia MIM#177170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13675 COL9A2 Ain Roesley Gene: col9a2 has been classified as Green List (High Evidence).
Mendeliome v0.13675 COL9A2 Ain Roesley Phenotypes for gene: COL9A2 were changed from to Stickler syndrome, type V MIM#614284' Epiphyseal dysplasia, multiple, 2 MIM#600204
Mendeliome v0.13674 COL9A2 Ain Roesley reviewed gene: COL9A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21671392, 31090205, 33356723, 10364514, 15633184, 20358595, 8528240; Phenotypes: Stickler syndrome, type V MIM#614284' Epiphyseal dysplasia, multiple, 2 MIM#600204; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13674 DYRK1B Krithika Murali reviewed gene: DYRK1B: Rating: AMBER; Mode of pathogenicity: None; Publications: 34193236, 34786696, 24827035, 28743892; Phenotypes: Abdominal obesity-metabolic syndrome 3 - MIM#615812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13674 COL6A3 Ain Roesley Gene: col6a3 has been classified as Green List (High Evidence).
Mendeliome v0.13673 COL6A2 Ain Roesley Gene: col6a2 has been classified as Green List (High Evidence).
Mendeliome v0.13671 COL6A1 Ain Roesley Gene: col6a1 has been classified as Green List (High Evidence).
Mendeliome v0.13669 COL5A2 Ain Roesley Gene: col5a2 has been classified as Green List (High Evidence).
Mendeliome v0.13670 COL5A2 Ain Roesley Phenotypes for gene: COL5A2 were changed from to Ehlers-Danlos syndrome, classic type, 2 MIM#130010
Mendeliome v0.13668 COL5A2 Ain Roesley reviewed gene: COL5A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301422; Phenotypes: Ehlers-Danlos syndrome, classic type, 2 MIM#130010; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13668 COL4A4 Ain Roesley Gene: col4a4 has been classified as Green List (High Evidence).
Mendeliome v0.13668 COL4A4 Ain Roesley Phenotypes for gene: COL4A4 were changed from to Alport syndrome 2, autosomal recessive MIM#203780; Hematuria, familial benign MIM#141200
Mendeliome v0.13666 COL4A4 Ain Roesley reviewed gene: COL4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301386; Phenotypes: Alport syndrome 2, autosomal recessive MIM#203780, Hematuria, familial benign MIM#141200; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13666 COL4A3 Ain Roesley Gene: col4a3 has been classified as Green List (High Evidence).
Mendeliome v0.13666 COL4A3 Ain Roesley Phenotypes for gene: COL4A3 were changed from to Alport syndrome 2, autosomal recessive, MIM# 203780; Alport syndrome 3, autosomal dominant, MIM# 104200
Mendeliome v0.13665 COL4A3 Ain Roesley reviewed gene: COL4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 2, autosomal recessive, MIM# 203780, Alport syndrome 3, autosomal dominant, MIM# 104200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13665 COL4A2 Ain Roesley Gene: col4a2 has been classified as Green List (High Evidence).
Mendeliome v0.13664 COL4A1 Ain Roesley Gene: col4a1 has been classified as Green List (High Evidence).
Mendeliome v0.13662 HMOX1 Zornitza Stark Gene: hmox1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13659 HMOX1 Zornitza Stark Classified gene: HMOX1 as Amber List (moderate evidence)
Mendeliome v0.13659 HMOX1 Zornitza Stark Gene: hmox1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13658 COL27A1 Ain Roesley Gene: col27a1 has been classified as Green List (High Evidence).
Mendeliome v0.13656 COL1A2 Ain Roesley edited their review of gene: COL1A2: Changed phenotypes: Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120, Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821, Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320, Osteogenesis imperfecta, type II, MIM# 166210, Osteogenesis imperfecta, type III, MIM# 259420, Osteogenesis imperfecta, type IV, MIM# 166220
Mendeliome v0.13656 COL1A2 Ain Roesley Gene: col1a2 has been classified as Green List (High Evidence).
Mendeliome v0.13656 COL1A2 Ain Roesley Phenotypes for gene: COL1A2 were changed from to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120; Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821; Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320; Osteogenesis imperfecta, type II, MIM# 166210; Osteogenesis imperfecta, type III, MIM# 259420; Osteogenesis imperfecta, type IV, MIM# 166220
Mendeliome v0.13653 COL1A2 Ain Roesley reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306229, 32091183, 2993307, 30821104; Phenotypes: Ehlers-Danlos syndrome, arthrochalasia type, 2 MIM#617821, Ehlers-Danlos syndrome, cardiac valvular type MIM#225320; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13653 COL1A1 Ain Roesley changed review comment from: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667)

The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985).; to: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667)

For skeletal phenotypes:
The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985).
Mendeliome v0.13653 COL1A1 Ain Roesley changed review comment from: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667); to: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667)

The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985).
Mendeliome v0.13653 COL1A1 Ain Roesley Gene: col1a1 has been classified as Green List (High Evidence).
Mendeliome v0.13653 COL1A1 Ain Roesley Phenotypes for gene: COL1A1 were changed from to Caffey disease MIM#114000; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MIM#619115; Ehlers-Danlos syndrome, arthrochalasia type, 1 MIM#130060; Osteogenesis imperfecta, type I MIM#166200; Osteogenesis imperfecta, type II MIM#166210; Osteogenesis imperfecta, type III MIM#259420; Osteogenesis imperfecta, type IV MIM#166220
Mendeliome v0.13652 COL1A1 Ain Roesley reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301422, 20301667, 30071989, 28981071, 12362985, 28956891; Phenotypes: Caffey disease MIM#114000, Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MIM#619115, Ehlers-Danlos syndrome, arthrochalasia type, 1 MIM#130060, Osteogenesis imperfecta, type I MIM#166200, Osteogenesis imperfecta, type II MIM#166210, Osteogenesis imperfecta, type III MIM#259420, Osteogenesis imperfecta, type IV MIM#166220; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13652 COL18A1 Ain Roesley Gene: col18a1 has been classified as Green List (High Evidence).
Mendeliome v0.13650 COL17A1 Ain Roesley Gene: col17a1 has been classified as Green List (High Evidence).
Mendeliome v0.13650 COL17A1 Ain Roesley Phenotypes for gene: COL17A1 were changed from to Epidermolysis bullosa, junctional 4, intermediate MIM#619787; Epithelial recurrent erosion dystrophy MIM#122400
Mendeliome v0.13649 COL17A1 Ain Roesley commented on gene: COL17A1: For Epithelial recurrent erosion dystrophy, AD:
Multiple families reported, c.3156C>T is recurrent.

For EB, AR:
well established association (GeneReviews PMID:20301304)
Mendeliome v0.13649 COL17A1 Ain Roesley reviewed gene: COL17A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27309958, 29708937, 25676728, 20301304; Phenotypes: Epidermolysis bullosa, junctional 4, intermediate MIM#619787, Epithelial recurrent erosion dystrophy MIM#122400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13649 COL12A1 Ain Roesley Gene: col12a1 has been classified as Green List (High Evidence).
Mendeliome v0.13647 COL11A2 Ain Roesley Gene: col11a2 has been classified as Green List (High Evidence).
Mendeliome v0.13647 COL11A2 Ain Roesley Phenotypes for gene: COL11A2 were changed from to Stickler syndrome type 3; Deafness, autosomal dominant 13 MIM#601868; Deafness, autosomal recessive 53 MIM#609706; Fibrochondrogenesis 2 MIM#614524; Otospondylomegaepiphyseal dysplasia, autosomal dominant MIM#184840; Otospondylomegaepiphyseal dysplasia, autosomal recessive MIM#215150
Mendeliome v0.13645 COL11A2 Ain Roesley reviewed gene: COL11A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10581026, 25633957, 16033917, 25240749, 22796475, 20112039; Phenotypes: Stickler syndrome type 3, Deafness, autosomal dominant 13 MIM#601868, Deafness, autosomal recessive 53 MIM#609706, Fibrochondrogenesis 2 MIM#614524, Otospondylomegaepiphyseal dysplasia, autosomal dominant MIM#184840, Otospondylomegaepiphyseal dysplasia, autosomal recessive MIM#215150; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13645 COG7 Ain Roesley Gene: cog7 has been classified as Green List (High Evidence).
Mendeliome v0.13643 COASY Ain Roesley Gene: coasy has been classified as Green List (High Evidence).
Mendeliome v0.13643 COASY Ain Roesley Phenotypes for gene: COASY were changed from to Neurodegeneration with brain iron accumulation 6 MIM#615643; Pontocerebellar hypoplasia, type 12 MIM#v618266
Mendeliome v0.13642 COASY Ain Roesley reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 30089828, 28489334, 24360804, 35499143; Phenotypes: Neurodegeneration with brain iron accumulation 6 MIM#615643, Pontocerebellar hypoplasia, type 12 MIM#v618266; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13642 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Mendeliome v0.13640 HK1 Zornitza Stark Gene: hk1 has been classified as Green List (High Evidence).
Mendeliome v0.13637 HK1 Zornitza Stark changed review comment from: HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy.

Founder variant in the Roma, -3818-195G-C, AltT2 EXON in 5'UTR identified in multiple families.

Note gene is associated with other phenotypes.; to: Bi-allelic variants and neuropathy: HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy.

Founder variant in the Roma, -3818-195G-C, AltT2 EXON in 5'UTR identified in multiple families.

Note gene is associated with other phenotypes.
Mendeliome v0.13636 RPE65 Zornitza Stark Gene: rpe65 has been classified as Green List (High Evidence).
Mendeliome v0.13636 RPE65 Zornitza Stark Phenotypes for gene: RPE65 were changed from to Leber congenital amaurosis 2 MIM#204100; Retinitis pigmentosa 20 MIM#613794; Retinitis pigmentosa 87 with choroidal involvement MIM#618697
Mendeliome v0.13633 SLC24A1 Zornitza Stark Gene: slc24a1 has been classified as Green List (High Evidence).
Mendeliome v0.13633 SLC24A1 Zornitza Stark Phenotypes for gene: SLC24A1 were changed from to Night blindness, congenital stationary (complete), 1D, autosomal recessive, MIM#613830, MONDO:0013450
Mendeliome v0.13630 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Green List (High Evidence).
Mendeliome v0.13627 RRAS Zornitza Stark Gene: rras has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13624 RRAS Zornitza Stark Classified gene: RRAS as Amber List (moderate evidence)
Mendeliome v0.13624 RRAS Zornitza Stark Gene: rras has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13623 SLC11A1 Zornitza Stark Gene: slc11a1 has been classified as Red List (Low Evidence).
Mendeliome v0.13623 SLC11A1 Zornitza Stark Phenotypes for gene: SLC11A1 were changed from to {Buruli ulcer, susceptibility to}, MIM#610446; {Mycobacterium tuberculosis, susceptibility to infection by} , MIM#607948
Mendeliome v0.13620 SLC11A1 Zornitza Stark Classified gene: SLC11A1 as Red List (low evidence)
Mendeliome v0.13620 SLC11A1 Zornitza Stark Gene: slc11a1 has been classified as Red List (Low Evidence).
Mendeliome v0.13619 LIPT2 Zornitza Stark reviewed gene: LIPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, MIM# 617668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13619 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Mendeliome v0.13619 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Mendeliome v0.13619 SIL1 Zornitza Stark Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome, MIM#248800; MONDO#0009567
Mendeliome v0.13618 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Mendeliome v0.13617 SIL1 Zornitza Stark Mode of inheritance for gene: SIL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13616 RPE65 Belinda Chong reviewed gene: RPE65: Rating: GREEN; Mode of pathogenicity: None; Publications: 14962443, 12960219, 11786058, 21654732, 27307694, 9501220, 16754667, 15557452; Phenotypes: Leber congenital amaurosis 2 MIM#204100, Retinitis pigmentosa 20 MIM#613794, Retinitis pigmentosa 87 with choroidal involvement MIM#618697; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13616 SLC24A1 Manny Jacobs reviewed gene: SLC24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35486108, 35446361, 20850105, 26822852; Phenotypes: Night blindness, congenital stationary (complete), 1D, autosomal recessive, MIM#613830, MONDO:0013450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13616 SIK1 Zornitza Stark Marked gene: SIK1 as ready
Mendeliome v0.13616 SIK1 Zornitza Stark Gene: sik1 has been classified as Green List (High Evidence).
Mendeliome v0.13616 SIK1 Zornitza Stark Phenotypes for gene: SIK1 were changed from to Developmental and epileptic encephalopathy 30, MIM#616341; developmental and epileptic encephalopathy, MONDO#0100062
Mendeliome v0.13615 SIK1 Zornitza Stark Publications for gene: SIK1 were set to
Mendeliome v0.13614 SIK1 Zornitza Stark Mode of inheritance for gene: SIK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13613 RRAS Belinda Chong changed review comment from: Catts et al (2021) identified a 7-year-old boy with a history of craniosynostosis, congenital heart defect, and mild dysmorphic features who was incidentally found to have pediatric MDS with monosomy 7 in the context of previously unrecognized germline RRAS mutation. A heterozygous c.116_118dup (NM_006270.5) variant resulting in p.G39dup was identified and excluded in an unaffected sibling, and both parents.

Two individuals reported. One de novo variant, the inheritance of the other variant uncertain. Some supportive functional data. Rated as LIMITED by ClinGen (reviewed 27/04/2018).; to: Catts et al (2021) identified a 7-year-old boy with a history of craniosynostosis, congenital heart defect, and mild dysmorphic features who was incidentally found to have pediatric MDS with monosomy 7 in the context of previously unrecognized germline RRAS mutation. A heterozygous c.116_118dup (NM_006270.5) variant resulting in p.G39dup was identified and excluded in an unaffected sibling, and both parents.

Two individuals reported. One de novo variant, the inheritance of the other variant uncertain. Some supportive functional data. Rated as LIMITED by ClinGen (reviewed 27/04/2018).
Mendeliome v0.13613 HIBCH Zornitza Stark Gene: hibch has been classified as Green List (High Evidence).
Mendeliome v0.13610 HGF Zornitza Stark Gene: hgf has been classified as Green List (High Evidence).
Mendeliome v0.13610 HGF Zornitza Stark Phenotypes for gene: HGF were changed from to Deafness, autosomal recessive 39, MIM# 608265
Mendeliome v0.13607 HGF Zornitza Stark reviewed gene: HGF: Rating: GREEN; Mode of pathogenicity: None; Publications: 19576567; Phenotypes: Deafness, autosomal recessive 39, MIM# 608265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13607 HGD Zornitza Stark Gene: hgd has been classified as Green List (High Evidence).
Mendeliome v0.13607 HGD Zornitza Stark Phenotypes for gene: HGD were changed from to Alkaptonuria MIM#203500; Disorders of phenylalanine or tyrosine metabolism
Mendeliome v0.13604 HFE Zornitza Stark Gene: hfe has been classified as Green List (High Evidence).
Mendeliome v0.13604 HFE Zornitza Stark Phenotypes for gene: HFE were changed from to Haemochromatosis, MIM# 235200
Mendeliome v0.13602 HFE Zornitza Stark reviewed gene: HFE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemochromatosis, MIM# 235200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13602 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Mendeliome v0.13602 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from to Growth hormone deficiency with pituitary anomalies, MIM#182230; Pituitary hormone deficiency, combined, 5, MIM#182230; Septooptic dysplasia, MIM#182230
Mendeliome v0.13600 HESX1 Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Growth hormone deficiency with pituitary anomalies, MIM#182230, Pituitary hormone deficiency, combined, 5, MIM#182230, Septooptic dysplasia, MIM#182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13599 SLC11A1 Samantha Ayres reviewed gene: SLC11A1: Rating: RED; Mode of pathogenicity: None; Publications: 35140349; Phenotypes: {Buruli ulcer, susceptibility to}, MIM#610446, {Mycobacterium tuberculosis, susceptibility to infection by} , MIM#607948; Mode of inheritance: Unknown
Mendeliome v0.13599 HERC1 Zornitza Stark Gene: herc1 has been classified as Green List (High Evidence).
Mendeliome v0.13596 HEPACAM Zornitza Stark Gene: hepacam has been classified as Green List (High Evidence).
Mendeliome v0.13593 LIPT2 Alison Yeung Gene: lipt2 has been classified as Green List (High Evidence).
Mendeliome v0.13593 LIPT2 Alison Yeung Phenotypes for gene: LIPT2 were changed from to Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, MIM#617668
Mendeliome v0.13592 SIL1 Samantha Ayres reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24176978, 16282977, 20301371; Phenotypes: Marinesco-Sjogren syndrome, MIM#248800, MONDO#0009567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13592 DNASE2 Zornitza Stark Phenotypes for gene: DNASE2 were changed from Auto-inflammatory disorder; splenomegaly; glomerulonephritis; liver fibrosis; arthritis; HLH to Autoinflammatory-pancytopaenia syndrome, MIM# 619858
Mendeliome v0.13589 LIPH Alison Yeung Gene: liph has been classified as Green List (High Evidence).
Mendeliome v0.13589 LIPH Alison Yeung Phenotypes for gene: LIPH were changed from to Woolly hair, autosomal recessive 2 with or without hypotrichosis, MIM# 604379; Hypotrichosis 7, MIM# 604379
Mendeliome v0.13588 LIPH Alison Yeung reviewed gene: LIPH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Woolly hair, autosomal recessive 2 with or without hypotrichosis, MIM# 604379, Hypotrichosis 7, MIM# 604379; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13587 LIPC Alison Yeung Gene: lipc has been classified as Green List (High Evidence).
Mendeliome v0.13583 LINS1 Alison Yeung Gene: lins1 has been classified as Green List (High Evidence).
Mendeliome v0.13583 LINS1 Alison Yeung Phenotypes for gene: LINS1 were changed from to Intellectual developmental disorder, autosomal recessive 27, MIM# 614340
Mendeliome v0.13581 HCRT Zornitza Stark Gene: hcrt has been classified as Red List (Low Evidence).
Mendeliome v0.13578 HCRT Zornitza Stark Classified gene: HCRT as Red List (low evidence)
Mendeliome v0.13578 HCRT Zornitza Stark Gene: hcrt has been classified as Red List (Low Evidence).
Mendeliome v0.13577 LIM2 Alison Yeung Gene: lim2 has been classified as Green List (High Evidence).
Mendeliome v0.13574 HCN1 Zornitza Stark Gene: hcn1 has been classified as Green List (High Evidence).
Mendeliome v0.13571 HCCS Zornitza Stark Gene: hccs has been classified as Green List (High Evidence).
Mendeliome v0.13568 HBA2 Zornitza Stark Gene: hba2 has been classified as Green List (High Evidence).
Mendeliome v0.13568 HBA2 Zornitza Stark Phenotypes for gene: HBA2 were changed from to Erythrocytosis 7, MIM# 617981; Heinz body anaemia, MIM# 140700; Haemoglobin H disease, deletional and nondeletional, MIM# 613978; Thalassaemia, alpha-, MIM# 604131
Mendeliome v0.13566 HBA2 Zornitza Stark reviewed gene: HBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Erythrocytosis 7, MIM# 617981, Heinz body anaemia, MIM# 140700, Haemoglobin H disease, deletional and nondeletional, MIM# 613978, Thalassaemia, alpha-, MIM# 604131; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13565 HBA1 Zornitza Stark Gene: hba1 has been classified as Green List (High Evidence).
Mendeliome v0.13565 HBA1 Zornitza Stark Phenotypes for gene: HBA1 were changed from to Erythrocytosis 7, MIM# 617981; Heinz body anemias, alpha-, MIM# 140700; Methemoglobinemia, alpha type , MIM#617973; Thalassemias, alpha-, MIM# 604131; Hemoglobin H disease, nondeletional, MIM# 613978
Mendeliome v0.13563 HBA1 Zornitza Stark reviewed gene: HBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Erythrocytosis 7, MIM# 617981, Heinz body anemias, alpha-, MIM# 140700, Methemoglobinemia, alpha type , MIM#617973, Thalassemias, alpha-, MIM# 604131, Hemoglobin H disease, nondeletional, MIM# 613978; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13563 HAO1 Zornitza Stark Gene: hao1 has been classified as Red List (Low Evidence).
Mendeliome v0.13563 HAO1 Zornitza Stark Classified gene: HAO1 as Red List (low evidence)
Mendeliome v0.13563 HAO1 Zornitza Stark Gene: hao1 has been classified as Red List (Low Evidence).
Mendeliome v0.13562 HAMP Zornitza Stark Gene: hamp has been classified as Green List (High Evidence).
Mendeliome v0.13562 HAMP Zornitza Stark Phenotypes for gene: HAMP were changed from to Haemochromatosis, type 2B, MIM# 613313
Mendeliome v0.13559 HAMP Zornitza Stark reviewed gene: HAMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 12469120, 34828384, 15198949; Phenotypes: Haemochromatosis, type 2B, MIM# 613313; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13559 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Mendeliome v0.13556 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Mendeliome v0.13554 HADH Zornitza Stark Gene: hadh has been classified as Green List (High Evidence).
Mendeliome v0.13552 HACD1 Zornitza Stark Gene: hacd1 has been classified as Green List (High Evidence).
Mendeliome v0.13549 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Mendeliome v0.13546 H6PD Zornitza Stark Gene: h6pd has been classified as Green List (High Evidence).
Mendeliome v0.13543 SIK1 Samantha Ayres reviewed gene: SIK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25839329, 27966542, 35267137; Phenotypes: Developmental and epileptic encephalopathy 30, MIM#616341, developmental and epileptic encephalopathy, MONDO#0100062; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.13543 BUD23 Zornitza Stark Gene: bud23 has been classified as Red List (Low Evidence).
Mendeliome v0.13543 BUD23 Zornitza Stark Classified gene: BUD23 as Red List (low evidence)
Mendeliome v0.13543 BUD23 Zornitza Stark Gene: bud23 has been classified as Red List (Low Evidence).
Mendeliome v0.13542 BTNL2 Zornitza Stark Gene: btnl2 has been classified as Red List (Low Evidence).
Mendeliome v0.13542 BTNL2 Zornitza Stark Phenotypes for gene: BTNL2 were changed from to {Sarcoidosis, susceptibility to, 2} 612387
Mendeliome v0.13540 BTNL2 Zornitza Stark Classified gene: BTNL2 as Red List (low evidence)
Mendeliome v0.13540 BTNL2 Zornitza Stark Gene: btnl2 has been classified as Red List (Low Evidence).
Mendeliome v0.13539 BTNL2 Zornitza Stark reviewed gene: BTNL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Sarcoidosis, susceptibility to, 2} 612387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13539 BTK Zornitza Stark Gene: btk has been classified as Green List (High Evidence).
Mendeliome v0.13536 BRIP1 Zornitza Stark Gene: brip1 has been classified as Green List (High Evidence).
Mendeliome v0.13533 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Mendeliome v0.13529 BPGM Zornitza Stark Gene: bpgm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13529 BPGM Zornitza Stark Phenotypes for gene: BPGM were changed from to Erythrocytosis, familial, 8, MIM# 222800
Mendeliome v0.13526 BPGM Zornitza Stark Classified gene: BPGM as Amber List (moderate evidence)
Mendeliome v0.13526 BPGM Zornitza Stark Gene: bpgm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13525 BPGM Zornitza Stark reviewed gene: BPGM: Rating: AMBER; Mode of pathogenicity: None; Publications: 1421379, 27651169, 25015942; Phenotypes: Erythrocytosis, familial, 8, MIM# 222800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13525 BMPR1A Zornitza Stark Gene: bmpr1a has been classified as Green List (High Evidence).
Mendeliome v0.13525 BMPR1A Zornitza Stark Phenotypes for gene: BMPR1A were changed from to Polyposis, juvenile intestinal, MIM# 174900
Mendeliome v0.13522 BMPR1A Zornitza Stark reviewed gene: BMPR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11381269; Phenotypes: Polyposis, juvenile intestinal, MIM# 174900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13522 BLVRA Zornitza Stark Gene: blvra has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13519 BLVRA Zornitza Stark Classified gene: BLVRA as Amber List (moderate evidence)
Mendeliome v0.13519 BLVRA Zornitza Stark Gene: blvra has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13518 BLK Zornitza Stark Gene: blk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13515 BLK Zornitza Stark Classified gene: BLK as Amber List (moderate evidence)
Mendeliome v0.13515 BLK Zornitza Stark Gene: blk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13514 BHLHE41 Zornitza Stark Gene: bhlhe41 has been classified as Red List (Low Evidence).
Mendeliome v0.13512 BHLHE41 Zornitza Stark Classified gene: BHLHE41 as Red List (low evidence)
Mendeliome v0.13512 BHLHE41 Zornitza Stark Gene: bhlhe41 has been classified as Red List (Low Evidence).
Mendeliome v0.13511 BFSP1 Zornitza Stark Gene: bfsp1 has been classified as Green List (High Evidence).
Mendeliome v0.13508 BCL2 Zornitza Stark Gene: bcl2 has been classified as Red List (Low Evidence).
Mendeliome v0.13508 BCL2 Zornitza Stark Classified gene: BCL2 as Red List (low evidence)
Mendeliome v0.13508 BCL2 Zornitza Stark Gene: bcl2 has been classified as Red List (Low Evidence).
Mendeliome v0.13507 BCKDK Zornitza Stark Gene: bckdk has been classified as Green List (High Evidence).
Mendeliome v0.13504 BCL10 Zornitza Stark Gene: bcl10 has been classified as Green List (High Evidence).
Mendeliome v0.13501 BCHE Zornitza Stark Gene: bche has been classified as Green List (High Evidence).
Mendeliome v0.13499 BBS2 Zornitza Stark Gene: bbs2 has been classified as Green List (High Evidence).
Mendeliome v0.13496 BBS12 Zornitza Stark Gene: bbs12 has been classified as Green List (High Evidence).
Mendeliome v0.13493 BBS10 Zornitza Stark Gene: bbs10 has been classified as Green List (High Evidence).
Mendeliome v0.13490 BBS1 Zornitza Stark Gene: bbs1 has been classified as Green List (High Evidence).
Mendeliome v0.13487 BAG3 Zornitza Stark Gene: bag3 has been classified as Green List (High Evidence).
Mendeliome v0.13484 BACH2 Zornitza Stark Gene: bach2 has been classified as Green List (High Evidence).
Mendeliome v0.13481 B4GALT1 Zornitza Stark Gene: b4galt1 has been classified as Green List (High Evidence).
Mendeliome v0.13478 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Green List (High Evidence).
Mendeliome v0.13478 B4GALNT1 Zornitza Stark Phenotypes for gene: B4GALNT1 were changed from to Spastic paraplegia 26, autosomal recessive (MIM #609195)
Mendeliome v0.13474 B4GALNT1 Zornitza Stark reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746551 24103911; Phenotypes: Spastic paraplegia 26, autosomal recessive (MIM #609195); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13474 B3GLCT Zornitza Stark Gene: b3glct has been classified as Green List (High Evidence).
Mendeliome v0.13471 APOA5 Zornitza Stark Gene: apoa5 has been classified as Green List (High Evidence).
Mendeliome v0.13469 APCDD1 Zornitza Stark Gene: apcdd1 has been classified as Green List (High Evidence).
Mendeliome v0.13469 APCDD1 Zornitza Stark Phenotypes for gene: APCDD1 were changed from to Hypotrichosis 1, MIM#605389
Mendeliome v0.13466 APCDD1 Zornitza Stark reviewed gene: APCDD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypotrichosis 1, MIM#605389; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13466 ANO10 Zornitza Stark Phenotypes for gene: ANO10 were changed from Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 to Spinocerebellar ataxia, autosomal recessive 10, MIM#613728
Mendeliome v0.13464 ANO10 Zornitza Stark reviewed gene: ANO10: Rating: GREEN; Mode of pathogenicity: None; Publications: 21092923, 25182700; Phenotypes: Spinocerebellar ataxia, autosomal recessive 10, MIM#613728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13464 PHOX2B Zornitza Stark Gene: phox2b has been classified as Green List (High Evidence).
Mendeliome v0.13461 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Mendeliome v0.13461 PEX26 Zornitza Stark Phenotypes for gene: PEX26 were changed from to Peroxisome biogenesis disorder 7A (Zellweger) - MIM#614872; Peroxisome biogenesis disorder 7B - MIM#614873
Mendeliome v0.13458 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Mendeliome v0.13458 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from to Peroxisome biogenesis disorder 5A (Zellweger) - MIM#614866; Peroxisome biogenesis disorder 5B - MIM#614867
Mendeliome v0.13455 PEX19 Zornitza Stark Gene: pex19 has been classified as Green List (High Evidence).
Mendeliome v0.13455 PEX19 Zornitza Stark Phenotypes for gene: PEX19 were changed from to Peroxisome biogenesis disorder 12A (Zellweger) - MIM#614886
Mendeliome v0.13454 PEX16 Zornitza Stark Gene: pex16 has been classified as Green List (High Evidence).
Mendeliome v0.13454 PEX16 Zornitza Stark Phenotypes for gene: PEX16 were changed from to Peroxisome biogenesis disorder 8A (Zellweger) - MIM#614876; Peroxisome biogenesis disorder 8B - MIM#614877
Mendeliome v0.13451 PEX14 Zornitza Stark Gene: pex14 has been classified as Green List (High Evidence).
Mendeliome v0.13451 PEX14 Zornitza Stark Phenotypes for gene: PEX14 were changed from to Peroxisome biogenesis disorder 13A (Zellweger) - MIM#614887
Mendeliome v0.13448 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Mendeliome v0.13448 PEX13 Zornitza Stark Phenotypes for gene: PEX13 were changed from to Peroxisome biogenesis disorder 11A (Zellweger) - MIM#614883; Peroxisome biogenesis disorder 11B - MIM#614885
Mendeliome v0.13446 PEX12 Zornitza Stark Gene: pex12 has been classified as Green List (High Evidence).
Mendeliome v0.13446 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from to Peroxisome biogenesis disorder 3A (Zellweger) - MIM#614859; Peroxisome biogenesis disorder 3B - MIM#266510
Mendeliome v0.13443 RSPH1 Zornitza Stark Gene: rsph1 has been classified as Green List (High Evidence).
Mendeliome v0.13443 RSPH1 Zornitza Stark Phenotypes for gene: RSPH1 were changed from to Ciliary dyskinesia, primary, 24 MIM#615481
Mendeliome v0.13437 APOA2 Elena Savva Gene: apoa2 has been classified as Red List (Low Evidence).
Mendeliome v0.13436 APOA2 Elena Savva Classified gene: APOA2 as Red List (low evidence)
Mendeliome v0.13436 APOA2 Elena Savva Gene: apoa2 has been classified as Red List (Low Evidence).
Mendeliome v0.13435 APOA1 Elena Savva Gene: apoa1 has been classified as Green List (High Evidence).
Mendeliome v0.13435 APOA1 Elena Savva Phenotypes for gene: APOA1 were changed from to Amyloidosis, 3 or more types MIM#105200; Hypoalphalipoproteinemia, primary, 2 MIM#618463; Hypoalphalipoproteinemia, primary, 2, intermediate MIM#619836
Mendeliome v0.13434 APOA1 Elena Savva reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, 3 or more types MIM#105200, Hypoalphalipoproteinemia, primary, 2 MIM#618463, Hypoalphalipoproteinemia, primary, 2, intermediate MIM#619836; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13434 AP1S2 Elena Savva Gene: ap1s2 has been classified as Green List (High Evidence).
Mendeliome v0.13432 APCDD1 Elena Savva reviewed gene: APCDD1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 22512811; Phenotypes: Hypotrichosis 1 MIM#605389; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.13432 ANO10 Elena Savva Phenotypes for gene: ANO10 were changed from Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 to Spinocerebellar ataxia, autosomal recessive 10 MIM#613728
Mendeliome v0.13430 ANO10 Elena Savva Phenotypes for gene: ANO10 were changed from to Spinocerebellar ataxia, autosomal recessive 10 MIM#613728
Mendeliome v0.13430 ANO10 Elena Savva Gene: ano10 has been classified as Green List (High Evidence).
Mendeliome v0.13429 PEX26 Krithika Murali reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: None; Publications: 12717447, 15858711, 17336976; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger) - MIM#614872, Peroxisome biogenesis disorder 7B - MIM#614873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13429 PEX2 Krithika Murali reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 14630978, 10528859, 23430938, 1546315; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger) - MIM#614866, Peroxisome biogenesis disorder 5B - MIM#614867; Mode of inheritance: None
Mendeliome v0.13429 PEX19 Krithika Murali reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: None; Publications: 10051604, 20683989, 11883941, 28391327; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger) - MIM#614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13429 PEX16 Krithika Murali reviewed gene: PEX16: Rating: GREEN; Mode of pathogenicity: None; Publications: 20647552, 12223482, 9837814, 11890679; Phenotypes: Peroxisome biogenesis disorder 8A (Zellweger) - MIM#614876, Peroxisome biogenesis disorder 8B - MIM#614877; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13429 PEX14 Krithika Murali reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: None; Publications: 18285423, 26627464, 21686775, 15146459; Phenotypes: Peroxisome biogenesis disorder 13A (Zellweger) - MIM#614887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13429 PEX13 Krithika Murali reviewed gene: PEX13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 11A (Zellweger) - MIM#614883, Peroxisome biogenesis disorder 11B - MIM#614885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13429 PEX12 Krithika Murali reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger) - MIM#614859, Peroxisome biogenesis disorder 3B - MIM#266510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13429 DIO1 Zornitza Stark Gene: dio1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13427 DIO1 Zornitza Stark Classified gene: DIO1 as Amber List (moderate evidence)
Mendeliome v0.13427 DIO1 Zornitza Stark Gene: dio1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13426 TUBA8 Zornitza Stark Phenotypes for gene: TUBA8 were changed from Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180 to Macrothrombocytopaenia, isolated, 2, autosomal dominant, MIM# 619840
Mendeliome v0.13423 TUBA8 Zornitza Stark Classified gene: TUBA8 as Amber List (moderate evidence)
Mendeliome v0.13423 TUBA8 Zornitza Stark Gene: tuba8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13422 TUBA8 Zornitza Stark changed review comment from: Two families reported initially (PMID 19896110). However, note that mouse model does not have a brain phenotype and WES in the original families identified homozygous, previously reported as pathogenic, LoF variant in SNAP29, which is much more likely to be causative (28388629).; to: Bi-allelic variants and cortical dysplasia: Two families reported initially (PMID 19896110). However, note that mouse model does not have a brain phenotype and WES in the original families identified homozygous, previously reported as pathogenic, LoF variant in SNAP29, which is much more likely to be causative (28388629).
Mendeliome v0.13420 PEX3 Zornitza Stark Gene: pex3 has been classified as Green List (High Evidence).
Mendeliome v0.13420 PEX3 Zornitza Stark Phenotypes for gene: PEX3 were changed from to Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882; Peroxisome biogenesis disorder 10B , MIM# 617370
Mendeliome v0.13417 PEX3 Zornitza Stark reviewed gene: PEX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10942428, 10958759, 10968777, 27557811, 33101983; Phenotypes: Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882, Peroxisome biogenesis disorder 10B , MIM# 617370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13417 PEX5 Zornitza Stark Gene: pex5 has been classified as Green List (High Evidence).
Mendeliome v0.13417 PEX5 Zornitza Stark Phenotypes for gene: PEX5 were changed from to Peroxisome biogenesis disorder 2A (Zellweger), MIM# 214110; Peroxisome biogenesis disorder 2B, MIM# 202370; Rhizomelic chondrodysplasia punctata, type 5, MIM# 616716
Mendeliome v0.13414 PEX5 Zornitza Stark reviewed gene: PEX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 7719337, 26220973, 20301621; Phenotypes: Peroxisome biogenesis disorder 2A (Zellweger), MIM# 214110, Peroxisome biogenesis disorder 2B, MIM# 202370, Rhizomelic chondrodysplasia punctata, type 5, MIM# 616716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13414 PEX7 Zornitza Stark Gene: pex7 has been classified as Green List (High Evidence).
Mendeliome v0.13414 PEX7 Zornitza Stark Phenotypes for gene: PEX7 were changed from to Peroxisome biogenesis disorder 9B, MIM# 614879; Rhizomelic chondrodysplasia punctata, type 1, MIM# 215100
Mendeliome v0.13411 PEX7 Zornitza Stark edited their review of gene: PEX7: Added comment: Well established gene-disease associations.; Changed publications: 11781871, 12522768, 12325024; Changed phenotypes: Peroxisome biogenesis disorder 9B, MIM# 614879, Rhizomelic chondrodysplasia punctata, type 1, MIM# 215100
Mendeliome v0.13411 PFKM Zornitza Stark Gene: pfkm has been classified as Green List (High Evidence).
Mendeliome v0.13408 PGAM2 Zornitza Stark Gene: pgam2 has been classified as Green List (High Evidence).
Mendeliome v0.13405 PHF11 Zornitza Stark Gene: phf11 has been classified as Red List (Low Evidence).
Mendeliome v0.13405 PHF11 Zornitza Stark Classified gene: PHF11 as Red List (low evidence)
Mendeliome v0.13405 PHF11 Zornitza Stark Gene: phf11 has been classified as Red List (Low Evidence).
Mendeliome v0.13404 PHIP Zornitza Stark Gene: phip has been classified as Green List (High Evidence).
Mendeliome v0.13401 PHIP Zornitza Stark changed review comment from: Chung-Jansen syndrome (CHUJANS) is characterized by global developmental delay apparent from infancy, impaired intellectual development or learning difficulties, behavioral abnormalities, dysmorphic features, and obesity.

More than 20 individuals reported.; to: Chung-Jansen syndrome (CHUJANS) is characterized by global developmental delay apparent from infancy, impaired intellectual development or learning difficulties, behavioural abnormalities, dysmorphic features, and obesity.

More than 20 individuals reported.
Mendeliome v0.13401 PHKA2 Zornitza Stark Gene: phka2 has been classified as Green List (High Evidence).
Mendeliome v0.13398 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Mendeliome v0.13393 PHYH Zornitza Stark Gene: phyh has been classified as Green List (High Evidence).
Mendeliome v0.13390 PHYH Zornitza Stark edited their review of gene: PHYH: Added comment: Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells.

Well established gene-disease association.; Changed publications: 9326939, 9326940
Mendeliome v0.13390 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Mendeliome v0.13390 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from to Marden-Walker syndrome (MIM#248700); Arthrogryposis, distal, type 3 (MIM#114300); Arthrogryposis, distal, type 5 (MIM#108145); Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146
Mendeliome v0.13387 PIEZO2 Zornitza Stark edited their review of gene: PIEZO2: Changed phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145), Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146
Mendeliome v0.13387 RSPH1 Belinda Chong reviewed gene: RSPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993197; Phenotypes: Ciliary dyskinesia, primary, 24 MIM#615481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13387 PIEZO2 Zornitza Stark reviewed gene: PIEZO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27653382, 27607563, 27843126, 27974811; Phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13387 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Green List (High Evidence).
Mendeliome v0.13387 BSCL2 Zornitza Stark Phenotypes for gene: BSCL2 were changed from to Neuropathy, distal hereditary motor, type VC, MIM# 619112; Encephalopathy, progressive, with or without lipodystrophy, MIM#615924; Lipodystrophy, congenital generalized, type 2, MIM# 269700; Silver spastic paraplegia syndrome, MIM# 270685; Developmental and epileptic encephalopathy, BSCL2-related, dominant, MONDO:0100062
Mendeliome v0.13384 BSCL2 Zornitza Stark edited their review of gene: BSCL2: Added comment: Multiple families reported with bi-allelic variants and isolated or syndromic lipodystrophy.

Mono-allelic variants and DEE: Two families reported with de novo variants in PMIDs 31369919 and 35290466. We are aware of further three individuals identified as a result of clinical testing, so a total of 4 with a change at position p.Pro149; Changed publications: 14981520, 15732094, 11479539, 15181077, 15126564, 23564749, 31369919, 35290466
Mendeliome v0.13384 BSCL2 Zornitza Stark edited their review of gene: BSCL2: Changed phenotypes: Neuropathy, distal hereditary motor, type VC, MIM# 619112, Encephalopathy, progressive, with or without lipodystrophy, MIM#615924, Lipodystrophy, congenital generalized, type 2, MIM# 269700, Silver spastic paraplegia syndrome, MIM# 270685, Developmental and epileptic encephalopathy, BSCL2-related, dominant, MONDO:0100062; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13384 CNNM2 Ain Roesley Gene: cnnm2 has been classified as Green List (High Evidence).
Mendeliome v0.13382 PIGC Zornitza Stark Gene: pigc has been classified as Green List (High Evidence).
Mendeliome v0.13382 PIGC Zornitza Stark Phenotypes for gene: PIGC were changed from to Glycosylphosphatidylinositol biosynthesis defect 16, MIM# 617816
Mendeliome v0.13379 PIGC Zornitza Stark reviewed gene: PIGC: Rating: GREEN; Mode of pathogenicity: None; Publications: 27694521, 32707268; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 16, MIM# 617816; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13379 CNGB1 Ain Roesley Gene: cngb1 has been classified as Green List (High Evidence).
Mendeliome v0.13377 CNGA1 Ain Roesley Gene: cnga1 has been classified as Green List (High Evidence).
Mendeliome v0.13375 CLN8 Ain Roesley Gene: cln8 has been classified as Green List (High Evidence).
Mendeliome v0.13375 CLN8 Ain Roesley Phenotypes for gene: CLN8 were changed from to Ceroid lipofuscinosis, neuronal, 8, MIM# 600143; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003
Mendeliome v0.13374 CLN8 Ain Roesley reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: 10508524, 15024724, 16570191; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, MIM# 600143, Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13374 CLN6 Ain Roesley Gene: cln6 has been classified as Green List (High Evidence).
Mendeliome v0.13374 CLN6 Ain Roesley Phenotypes for gene: CLN6 were changed from to Ceroid lipofuscinosis, neuronal, 6, MIM# 601780; Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, MIM# 204300
Mendeliome v0.13372 CLN6 Ain Roesley reviewed gene: CLN6: Rating: GREEN; Mode of pathogenicity: None; Publications: 11791207, 11727201, 21549341, 30561534; Phenotypes: Ceroid lipofuscinosis, neuronal, 6, MIM# 601780, Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, MIM# 204300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13372 CLEC7A Ain Roesley Gene: clec7a has been classified as Red List (Low Evidence).
Mendeliome v0.13372 CLEC7A Ain Roesley Phenotypes for gene: CLEC7A were changed from to {Aspergillosis, susceptibility to} MIM#614079; candidiasis, familial, 4, autosomal recessive MIM#613108
Mendeliome v0.13371 CLEC7A Ain Roesley Classified gene: CLEC7A as Red List (low evidence)
Mendeliome v0.13371 CLEC7A Ain Roesley Gene: clec7a has been classified as Red List (Low Evidence).
Mendeliome v0.13370 CLEC7A Ain Roesley edited their review of gene: CLEC7A: Changed publications: 19864674, 20807886; Changed phenotypes: {Aspergillosis, susceptibility to} MIM#614079, candidiasis, familial, 4, autosomal recessive MIM#613108; Set current diagnostic: yes
Mendeliome v0.13370 CLEC7A Ain Roesley changed review comment from: Unable to find any mendelian disease association; to: Unable to find any mendelian disease association.

Reports of Tyr238* and it's association with {Aspergillosis, susceptibility to} MIM#614079 leading to candidiasis, familial, 4, autosomal recessive MIM#613108
Mendeliome v0.13370 PIGW Zornitza Stark Gene: pigw has been classified as Green List (High Evidence).
Mendeliome v0.13370 PIGW Zornitza Stark Phenotypes for gene: PIGW were changed from to Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025
Mendeliome v0.13367 PIGW Zornitza Stark reviewed gene: PIGW: Rating: GREEN; Mode of pathogenicity: None; Publications: 24367057, 27626616, 30813920, 32198969; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13367 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Green List (High Evidence).
Mendeliome v0.13364 PITX2 Zornitza Stark Gene: pitx2 has been classified as Green List (High Evidence).
Mendeliome v0.13364 PITX2 Zornitza Stark Phenotypes for gene: PITX2 were changed from to Anterior segment dysgenesis 4, MIM# 137600; Axenfeld-Rieger syndrome, type 1, MIM# 180500
Mendeliome v0.13361 PITX2 Zornitza Stark reviewed gene: PITX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32499604, 32400113, 31341655, 31185933, 30457409; Phenotypes: Anterior segment dysgenesis 4, MIM# 137600, Axenfeld-Rieger syndrome, type 1, MIM# 180500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13361 PITX3 Zornitza Stark Gene: pitx3 has been classified as Green List (High Evidence).
Mendeliome v0.13361 PITX3 Zornitza Stark Phenotypes for gene: PITX3 were changed from Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia to Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia MONDO:0021129
Mendeliome v0.13360 PITX3 Zornitza Stark Phenotypes for gene: PITX3 were changed from to Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia
Mendeliome v0.13357 PITX3 Zornitza Stark reviewed gene: PITX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29405783; Phenotypes: Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250, Cataract 11, multiple types, MIM# 610623, Microphthalmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13356 PEX11B Zornitza Stark Gene: pex11b has been classified as Green List (High Evidence).
Mendeliome v0.13356 PEX11B Zornitza Stark Phenotypes for gene: PEX11B were changed from to Peroxisome biogenesis disorder 14B - MIM#614920
Mendeliome v0.13353 PER2 Zornitza Stark Gene: per2 has been classified as Red List (Low Evidence).
Mendeliome v0.13350 PER2 Zornitza Stark Classified gene: PER2 as Red List (low evidence)
Mendeliome v0.13350 PER2 Zornitza Stark Gene: per2 has been classified as Red List (Low Evidence).
Mendeliome v0.13349 PDZD7 Zornitza Stark Gene: pdzd7 has been classified as Green List (High Evidence).
Mendeliome v0.13349 PDZD7 Zornitza Stark Phenotypes for gene: PDZD7 were changed from to Deafness, autosomal recessive 57, MIM# 618003; Usher syndrome, type IIC, GPR98/PDZD7 digenic, MIM# 605472
Mendeliome v0.13346 PDYN Zornitza Stark Gene: pdyn has been classified as Green List (High Evidence).
Mendeliome v0.13343 PDGFRA Zornitza Stark Gene: pdgfra has been classified as Green List (High Evidence).
Mendeliome v0.13340 RSPH3 Zornitza Stark Gene: rsph3 has been classified as Green List (High Evidence).
Mendeliome v0.13340 RSPH3 Zornitza Stark Phenotypes for gene: RSPH3 were changed from to Ciliary dyskinesia, primary, 32 MIM#616481
Mendeliome v0.13337 EIF2AK2 Zornitza Stark edited their review of gene: EIF2AK2: Changed phenotypes: Dystonia 33, MIM# 619687, Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13337 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Green List (High Evidence).
Mendeliome v0.13337 RSPH4A Zornitza Stark Phenotypes for gene: RSPH4A were changed from to Ciliary dyskinesia, primary, 11, OMIM#612649
Mendeliome v0.13334 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Green List (High Evidence).
Mendeliome v0.13334 RSPH9 Zornitza Stark Phenotypes for gene: RSPH9 were changed from to Ciliary dyskinesia, primary, 12, MIM#612650
Mendeliome v0.13331 BVES Zornitza Stark Gene: bves has been classified as Green List (High Evidence).
Mendeliome v0.13331 BVES Zornitza Stark Phenotypes for gene: BVES were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 25, MIM# 616812
Mendeliome v0.13327 BVES Zornitza Stark reviewed gene: BVES: Rating: GREEN; Mode of pathogenicity: None; Publications: 26642364, 32528171, 31119192; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 25, MIM# 616812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13326 CLDN19 Ain Roesley Gene: cldn19 has been classified as Green List (High Evidence).
Mendeliome v0.13324 CLDN16 Ain Roesley Gene: cldn16 has been classified as Green List (High Evidence).
Mendeliome v0.13324 CLDN16 Ain Roesley Phenotypes for gene: CLDN16 were changed from to Hypomagnesemia 3, renal MIM#248250; amelogenesis imperfecta MONDO#0019507, CLDN16-related
Mendeliome v0.13323 CLDN16 Ain Roesley reviewed gene: CLDN16: Rating: GREEN; Mode of pathogenicity: None; Publications: 26426912, 16501001, 10878661, 32869508; Phenotypes: Hypomagnesemia 3, renal MIM#248250, amelogenesis imperfecta MONDO#0019507, CLDN16-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13323 CLDN1 Ain Roesley Gene: cldn1 has been classified as Green List (High Evidence).
Mendeliome v0.13324 CLDN1 Ain Roesley Phenotypes for gene: CLDN1 were changed from to Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis MIM#607626
Mendeliome v0.13322 CLDN1 Ain Roesley reviewed gene: CLDN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12164927, 11889141, 29146216; Phenotypes: Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis MIM#607626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13322 CLCNKB Ain Roesley Gene: clcnkb has been classified as Green List (High Evidence).
Mendeliome v0.13320 CLCF1 Ain Roesley Gene: clcf1 has been classified as Green List (High Evidence).
Mendeliome v0.13318 PEX11B Krithika Murali reviewed gene: PEX11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621, 22581968; Phenotypes: Peroxisome biogenesis disorder 14B - MIM#614920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13318 CIT Ain Roesley Gene: cit has been classified as Green List (High Evidence).
Mendeliome v0.13317 CIT Ain Roesley Phenotypes for gene: CIT were changed from Microcephaly 17, primary, autosomal recessive (MIM#617090) to Microcephaly 17, primary, autosomal recessive (MIM#617090)
Mendeliome v0.13317 CIT Ain Roesley Phenotypes for gene: CIT were changed from to Microcephaly 17, primary, autosomal recessive (MIM#617090)
Mendeliome v0.13315 CIT Ain Roesley reviewed gene: CIT: Rating: GREEN; Mode of pathogenicity: None; Publications: 27453578, 27503289, 27453579; Phenotypes: Microcephaly 17, primary, autosomal recessive (MIM#617090); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13315 CISH Ain Roesley Gene: cish has been classified as Red List (Low Evidence).
Mendeliome v0.13315 CISH Ain Roesley Classified gene: CISH as Red List (low evidence)
Mendeliome v0.13315 CISH Ain Roesley Gene: cish has been classified as Red List (Low Evidence).
Mendeliome v0.13314 PDZD7 Krithika Murali reviewed gene: PDZD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 20440071, 19028668, 26416264, 26849169, 27068579, 26445815, 28173822l, 24334608; Phenotypes: Deafness, autosomal recessive 57, MIM# 618003, Usher syndrome, type IIC, GPR98/PDZD7 digenic, MIM# 605472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13314 CISD2 Ain Roesley Gene: cisd2 has been classified as Green List (High Evidence).
Mendeliome v0.13313 CILP Ain Roesley Gene: cilp has been classified as Red List (Low Evidence).
Mendeliome v0.13313 CILP Ain Roesley Classified gene: CILP as Red List (low evidence)
Mendeliome v0.13313 CILP Ain Roesley Gene: cilp has been classified as Red List (Low Evidence).
Mendeliome v0.13312 CIC Ain Roesley Gene: cic has been classified as Green List (High Evidence).
Mendeliome v0.13310 CHST14 Ain Roesley Gene: chst14 has been classified as Green List (High Evidence).
Mendeliome v0.13308 CHRNA2 Ain Roesley Gene: chrna2 has been classified as Green List (High Evidence).
Mendeliome v0.13306 CHRM2 Ain Roesley Gene: chrm2 has been classified as Red List (Low Evidence).
Mendeliome v0.13305 CHRM2 Ain Roesley Classified gene: CHRM2 as Red List (low evidence)
Mendeliome v0.13305 CHRM2 Ain Roesley Gene: chrm2 has been classified as Red List (Low Evidence).
Mendeliome v0.13304 CHN1 Ain Roesley Gene: chn1 has been classified as Green List (High Evidence).
Mendeliome v0.13301 CHMP4B Ain Roesley Gene: chmp4b has been classified as Green List (High Evidence).
Mendeliome v0.13299 CHM Ain Roesley Gene: chm has been classified as Green List (High Evidence).
Mendeliome v0.13298 CHIT1 Ain Roesley Phenotypes for gene: CHIT1 were changed from [Chitotriosidase deficiency] MIM#614122 to [Chitotriosidase deficiency] MIM#614122
Mendeliome v0.13297 CHIT1 Ain Roesley Phenotypes for gene: CHIT1 were changed from to [Chitotriosidase deficiency] MIM#614122
Mendeliome v0.13297 CHIT1 Ain Roesley Gene: chit1 has been classified as Red List (Low Evidence).
Mendeliome v0.13297 CHIT1 Ain Roesley Classified gene: CHIT1 as Red List (low evidence)
Mendeliome v0.13297 CHIT1 Ain Roesley Gene: chit1 has been classified as Red List (Low Evidence).
Mendeliome v0.13297 PDGFRA Krithika Murali changed review comment from: ?Suitability for Incidentalome versus Mendeliome based on adult age of diagnosis in reported cases.

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Six unrelated families reported with heterozygous germline variants associated with familial GIST and/or inflammatory fibroid polyps - IFP (benign lesions caused by excessive tissue proliferation and inflammatory cell infiltration into the lumen of the GI tract). Note that reported individuals diagnosed as adults. One individual reported with diagnosis of gastric mass/polyps age 22 (in 1977) raising the possibility of pre-symptomatic disease onset in adolescence. Green PanelApp England in the following panels: tumour predisposition - childhood onset; inherited predisposition to GIST; sarcoma cancer susceptibility.

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PMID 34107389 Hodan et al 2021 - report a 35 yo F with jejunal IFP and a heterozygous germline missense PDGFRA variant (c.1664A>G p.Y555C) . The variant segregated with 3 relatives with confirmed IFPs. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This variant was also reported in an unrelated family with multiple IFPs in 2006.

PMID 29486293 Manley et al 2018 - proband is a 50 yo M with multiple ileal intusussceptions and IFPs and GIST. Heterozygous D846V germline variant identified. Variant identified in daughter and 2 siblings. Coarser face, coarser skin, broader hands and feet, unexplained premature loss of teeth requiring dentures in their 40s described in relatives with the variant, no polyps or tumour identified in screened family members. Pdgfra +/K mutant mice recapitulated the human phenotype. Mice with the constitutively activated mutant PDGFRA shown to have diffuse expansion of the gastrointestinal submucosa, which exhibits an increased number of spindled fibroblast-like cells and marked collagen deposition. Mutant mice also develop intestinal polyps morphologically similar to IFPs. The Pdgfra +/K mice also exhibit thickened skin due to excess collagen deposition within the dermis and subcutaneous tissues.

PMID 25975287 Ricci et al 2015 - report a family with het germline P653L PDGFRA missense variant. The proband was a 67 yo M with multiple intra-abdominal GIST and gastric/colonic inflammatory fibroid polyps. Multiple adult relatives (youngest age 31) were diagnosed with IFPs/fibrous tumours with the variant segregating with disease.

PMID: 18670346 Carney et al 2008 and PMID: 17566086 Pasini et al 2007 - heterozygous germline PDGFRA mutation (V561D) in an individual with GIST and multiple polyps, diagnosed initially aged 22 with multiple GIST/polyps. No other relatives available for genotyping and no other significant family history reported.

PMID: 17087943 de Raedt et al 2006 - heterozygous PDGFRA(Y555C) variant reported in a family with multiple relatives affected by IFP, including one death from secondary bowel obstruction age 35.

PMID: 14699510 Chompret et al 2004 - Heterozygous c.2675G>T D846Y germline variant detected in a French family with 5 relatives developing adult-onset GIST, variant segregated with disease.

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Gain of function somatic variants associated with sporadic GIST. Somatic chromosomal rearrangements resulting in PDGFRA and FIP1L1 gene fusion associated with idiopathic hypereosinophilic syndrome.; to: Six unrelated families reported with heterozygous germline variants associated with familial GIST and/or inflammatory fibroid polyps - IFP (benign lesions caused by excessive tissue proliferation and inflammatory cell infiltration into the lumen of the GI tract). Note that reported individuals diagnosed as adults. One individual reported with diagnosis of gastric mass/polyps age 22 (in 1977) raising the possibility of pre-symptomatic disease onset in adolescence. Green PanelApp England in the following panels: tumour predisposition - childhood onset; inherited predisposition to GIST; sarcoma cancer susceptibility.

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PMID 34107389 Hodan et al 2021 - report a 35 yo F with jejunal IFP and a heterozygous germline missense PDGFRA variant (c.1664A>G p.Y555C) . The variant segregated with 3 relatives with confirmed IFPs. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This variant was also reported in an unrelated family with multiple IFPs in 2006.

PMID 29486293 Manley et al 2018 - proband is a 50 yo M with multiple ileal intusussceptions and IFPs and GIST. Heterozygous D846V germline variant identified. Variant identified in daughter and 2 siblings. Coarser face, coarser skin, broader hands and feet, unexplained premature loss of teeth requiring dentures in their 40s described in relatives with the variant, no polyps or tumour identified in screened family members. Pdgfra +/K mutant mice recapitulated the human phenotype. Mice with the constitutively activated mutant PDGFRA shown to have diffuse expansion of the gastrointestinal submucosa, which exhibits an increased number of spindled fibroblast-like cells and marked collagen deposition. Mutant mice also develop intestinal polyps morphologically similar to IFPs. The Pdgfra +/K mice also exhibit thickened skin due to excess collagen deposition within the dermis and subcutaneous tissues.

PMID 25975287 Ricci et al 2015 - report a family with het germline P653L PDGFRA missense variant. The proband was a 67 yo M with multiple intra-abdominal GIST and gastric/colonic inflammatory fibroid polyps. Multiple adult relatives (youngest age 31) were diagnosed with IFPs/fibrous tumours with the variant segregating with disease.

PMID: 18670346 Carney et al 2008 and PMID: 17566086 Pasini et al 2007 - heterozygous germline PDGFRA mutation (V561D) in an individual with GIST and multiple polyps, diagnosed initially aged 22 with multiple GIST/polyps. No other relatives available for genotyping and no other significant family history reported.

PMID: 17087943 de Raedt et al 2006 - heterozygous PDGFRA(Y555C) variant reported in a family with multiple relatives affected by IFP, including one death from secondary bowel obstruction age 35.

PMID: 14699510 Chompret et al 2004 - Heterozygous c.2675G>T D846Y germline variant detected in a French family with 5 relatives developing adult-onset GIST, variant segregated with disease.

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Gain of function somatic variants associated with sporadic GIST. Somatic chromosomal rearrangements resulting in PDGFRA and FIP1L1 gene fusion associated with idiopathic hypereosinophilic syndrome.
Mendeliome v0.13296 CHIT1 Ain Roesley reviewed gene: CHIT1: Rating: RED; Mode of pathogenicity: None; Publications: 23430794; Phenotypes: [Chitotriosidase deficiency] MIM#614122; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13296 CHD1 Ain Roesley Gene: chd1 has been classified as Green List (High Evidence).
Mendeliome v0.13294 CFP Ain Roesley Gene: cfp has been classified as Green List (High Evidence).
Mendeliome v0.13292 CFI Ain Roesley Gene: cfi has been classified as Green List (High Evidence).
Mendeliome v0.13292 CFI Ain Roesley Gene: cfi has been classified as Green List (High Evidence).
Mendeliome v0.13289 RSPH3 Belinda Chong reviewed gene: RSPH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26073779; Phenotypes: Ciliary dyskinesia, primary, 32 MIM#616481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13289 HSPG2 Zornitza Stark changed review comment from: Allelic disorders with some phenotypic overlap.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition defined by the association of myotonia with chondrodysplasia; blepharophimosis is a key feature. More than 20 families reported.

Silverman-Handmaker dyssegmental dysplasia (DDSH) is a lethal autosomal recessive skeletal dysplasia with anisospondyly and micromelia. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. The endochondral growth plate is short, the calcospherites (spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. Two families reported.; to: Allelic disorders with some phenotypic overlap.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition defined by the association of myotonia with chondrodysplasia; blepharophimosis is a key feature. More than 20 families reported.

Silverman-Handmaker dyssegmental dysplasia (DDSH) is a lethal autosomal recessive skeletal dysplasia with anisospondyly and micromelia. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. The endochondral growth plate is short, the calcospherites (spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. Two families reported. Appears associated with null variants.
Mendeliome v0.13289 PKD1 Zornitza Stark Gene: pkd1 has been classified as Green List (High Evidence).
Mendeliome v0.13287 PKD2 Zornitza Stark Gene: pkd2 has been classified as Green List (High Evidence).
Mendeliome v0.13285 PKLR Zornitza Stark Gene: pklr has been classified as Green List (High Evidence).
Mendeliome v0.13285 PKLR Zornitza Stark Phenotypes for gene: PKLR were changed from to Pyruvate kinase deficiency, MIM# 266200; Adenosine triphosphate, elevated, of erythrocytes, MIM# 102900
Mendeliome v0.13282 PKLR Zornitza Stark reviewed gene: PKLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 1896471, 9160692, 9057665, 16704447, 9090535; Phenotypes: Pyruvate kinase deficiency, MIM# 266200, Adenosine triphosphate, elevated, of erythrocytes, MIM# 102900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13282 PKP1 Zornitza Stark Gene: pkp1 has been classified as Green List (High Evidence).
Mendeliome v0.13282 PKP1 Zornitza Stark Phenotypes for gene: PKP1 were changed from to Ectodermal dysplasia/skin fragility syndrome, MIM# 604536
Mendeliome v0.13279 PKP1 Zornitza Stark reviewed gene: PKP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24073657, 16781314, 11994137, 10951270, 32346906; Phenotypes: Ectodermal dysplasia/skin fragility syndrome, MIM# 604536; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13279 PLA2G5 Zornitza Stark Gene: pla2g5 has been classified as Green List (High Evidence).
Mendeliome v0.13276 PLCE1 Zornitza Stark Gene: plce1 has been classified as Green List (High Evidence).
Mendeliome v0.13273 PLCG2 Zornitza Stark Gene: plcg2 has been classified as Green List (High Evidence).
Mendeliome v0.13269 PLEKHM1 Zornitza Stark Phenotypes for gene: PLEKHM1 were changed from Osteopetrosis, autosomal dominant 3, MIM# 618107 to Osteopetrosis, autosomal dominant 3, MIM# 618107; Osteopetrosis, autosomal recessive 6 , MIM# 611497
Mendeliome v0.13266 PLEKHM1 Zornitza Stark edited their review of gene: PLEKHM1: Changed publications: 27291868, 21054159, 17997709, 17404618, 28290981; Changed phenotypes: Osteopetrosis, autosomal dominant 3, MIM# 618107, Osteopetrosis, autosomal recessive 6 , MIM# 611497; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13266 PLEKHM1 Zornitza Stark Gene: plekhm1 has been classified as Green List (High Evidence).
Mendeliome v0.13266 PLEKHM1 Zornitza Stark Phenotypes for gene: PLEKHM1 were changed from to Osteopetrosis, autosomal dominant 3, MIM# 618107
Mendeliome v0.13263 PLEKHM1 Zornitza Stark reviewed gene: PLEKHM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27291868, 21054159, 17997709, 17404618; Phenotypes: Osteopetrosis, autosomal dominant 3, MIM# 618107; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13263 RSPH4A Belinda Chong changed review comment from: Radial spokes are regularly spaced along cilia, sperm, and flagella axonemes and have a multisubunit 'stalk' and 'head' that form a signal transduction scaffold between the central microtubule pair and dynein arms. RSPH4A is predicted to be a component of the radial spoke head based on homology with proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates (Castleman et al., 2009; PMID19200523)

9 families with primary ciliary dyskinesia without situs inversus (Kott et al. 2013 (PMID:23993197), Castleman et al., 2009 (PMID19200523) and Daniels et al. 2013; (PMID:23798057)):
- In affected members of 4 Pakistani families with CILD11, Castleman et al. (2009) identified a homozygous mutation in the RSPH4A gene.
- In affected members of a family of northern European descent with CILD11, Castleman et al. (2009) identified compound heterozygosity for 2 mutations in the RSPH4A gene
- Kott et al. (2013) identified pathogenic mutations in the RSPH4A gene in 7 (14%) of 48 families with a specific CILD.

Common founder mutation:
- Daniels et al. (2013) identified a common founder mutation in the RSPH4A gene in 9 patients with CILD11, all of whom had Puerto Rican ancestry.

Multiple individuals in ClinVar with primary ciliary dyskinesia; to: Radial spokes are regularly spaced along cilia, sperm, and flagella axonemes and have a multisubunit 'stalk' and 'head' that form a signal transduction scaffold between the central microtubule pair and dynein arms. RSPH4A is predicted to be a component of the radial spoke head based on homology with proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates (Castleman et al., 2009; PMID19200523)

9 families with primary ciliary dyskinesia without situs inversus (Kott et al. 2013 (PMID:23993197), Castleman et al., 2009 (PMID19200523) and Daniels et al. 2013; (PMID:23798057)):
- In affected members of 4 Pakistani families with CILD11, Castleman et al. (2009) identified a homozygous mutation in the RSPH4A gene.
- In affected members of a family of northern European descent with CILD11, Castleman et al. (2009) identified compound heterozygosity for 2 mutations in the RSPH4A gene
- Kott et al. (2013) identified pathogenic mutations in the RSPH4A gene in 7 (14%) of 48 families with a specific CILD.

Common founder mutation:
- Daniels et al. (2013) identified a common founder mutation in the RSPH4A gene in 9 patients with CILD11, all of whom had Puerto Rican ancestry.

Multiple individuals in ClinVar with primary ciliary dyskinesia

PMID: 25789548; Frommer 2015: 8 PCD families reported, only 4 different variants identified. Functional studies performed.

PMID: 22448264; Ziętkiewicz 2012: 4 additional families/variants reported.
Mendeliome v0.13263 RSPH4A Belinda Chong reviewed gene: RSPH4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23798057, 23798057, 23798057; Phenotypes: Ciliary dyskinesia, primary, 11 OMIM#612649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13263 RSPH9 Belinda Chong reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25789548, 22384920, 23993197, 19200523, 27626380; Phenotypes: Ciliary dyskinesia, primary, 12 MIM#612650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13263 PLN Zornitza Stark Gene: pln has been classified as Green List (High Evidence).
Mendeliome v0.13260 PLOD1 Zornitza Stark Gene: plod1 has been classified as Green List (High Evidence).
Mendeliome v0.13257 PLOD2 Zornitza Stark Gene: plod2 has been classified as Green List (High Evidence).
Mendeliome v0.13254 PMFBP1 Zornitza Stark Gene: pmfbp1 has been classified as Green List (High Evidence).
Mendeliome v0.13254 PMFBP1 Zornitza Stark Phenotypes for gene: PMFBP1 were changed from to Male infertility with teratozoospermia due to single gene mutation, MONDO:0018394
Mendeliome v0.13251 PMFBP1 Zornitza Stark reviewed gene: PMFBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33484382, 33452591, 32285443; Phenotypes: Male infertility with teratozoospermia due to single gene mutation, MONDO:0018394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13251 PMPCA Zornitza Stark Gene: pmpca has been classified as Green List (High Evidence).
Mendeliome v0.13251 PMPCA Zornitza Stark Phenotypes for gene: PMPCA were changed from to Spinocerebellar ataxia, autosomal recessive 2, MIM# 213200
Mendeliome v0.13248 PMPCA Zornitza Stark reviewed gene: PMPCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25808372, 26657514, 33272776, 30617178; Phenotypes: Spinocerebellar ataxia, autosomal recessive 2, MIM# 213200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13248 PMPCB Zornitza Stark Gene: pmpcb has been classified as Green List (High Evidence).
Mendeliome v0.13245 PMPCB Zornitza Stark changed review comment from: Progressive disorder, includes ataxia. Four unrelated families reported.; to: Progressive disorder. Four unrelated families reported.
Mendeliome v0.13245 PNPO Zornitza Stark Gene: pnpo has been classified as Green List (High Evidence).
Mendeliome v0.13242 PODXL Zornitza Stark Gene: podxl has been classified as Green List (High Evidence).
Mendeliome v0.13239 POFUT1 Zornitza Stark Gene: pofut1 has been classified as Green List (High Evidence).
Mendeliome v0.13236 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Mendeliome v0.13236 POLG Zornitza Stark Phenotypes for gene: POLG were changed from to Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450; Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640
Mendeliome v0.13233 POLG Zornitza Stark reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13233 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Mendeliome v0.13230 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Green List (High Evidence).
Mendeliome v0.13227 POMK Zornitza Stark Gene: pomk has been classified as Green List (High Evidence).
Mendeliome v0.13224 RAX2 Zornitza Stark Gene: rax2 has been classified as Green List (High Evidence).
Mendeliome v0.13221 RASA1 Zornitza Stark Gene: rasa1 has been classified as Green List (High Evidence).
Mendeliome v0.13220 PDX1 Zornitza Stark Gene: pdx1 has been classified as Green List (High Evidence).
Mendeliome v0.13220 PDX1 Zornitza Stark Phenotypes for gene: PDX1 were changed from to Pancreatic agenesis 1 - MIM#260370 (AR); MODY, type IV - MIM#606392(AD)
Mendeliome v0.13215 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
Mendeliome v0.13212 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Mendeliome v0.13210 RSPO1 Zornitza Stark Gene: rspo1 has been classified as Green List (High Evidence).
Mendeliome v0.13210 RSPO1 Zornitza Stark Phenotypes for gene: RSPO1 were changed from to Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal MIM#610644; Palmoplantar hyperkeratosis and true hermaphroditism MIM#610644
Mendeliome v0.13206 FAT1 Zornitza Stark Phenotypes for gene: FAT1 were changed from syndromic disease MONDO:0002254; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to syndromic disease MONDO:0002254, FAT1-related; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Mendeliome v0.13203 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Mendeliome v0.13200 PDE6H Zornitza Stark Gene: pde6h has been classified as Green List (High Evidence).
Mendeliome v0.13200 PDE6H Zornitza Stark Phenotypes for gene: PDE6H were changed from to Achromatopsia 6 - MIM#610024
Mendeliome v0.13197 PDE6G Zornitza Stark Gene: pde6g has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13194 PDE6G Zornitza Stark Classified gene: PDE6G as Amber List (moderate evidence)
Mendeliome v0.13194 PDE6G Zornitza Stark Gene: pde6g has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13193 PDE6C Zornitza Stark Gene: pde6c has been classified as Green List (High Evidence).
Mendeliome v0.13193 PDE6C Zornitza Stark Phenotypes for gene: PDE6C were changed from to Cone dystrophy 4, MIM# 613093; Achromatopsia-5
Mendeliome v0.13190 PDE6C Zornitza Stark reviewed gene: PDE6C: Rating: GREEN; Mode of pathogenicity: None; Publications: 19615668, 30080950; Phenotypes: Cone dystrophy 4, MIM# 613093, Achromatopsia-5; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13190 PDE6B Zornitza Stark Gene: pde6b has been classified as Green List (High Evidence).
Mendeliome v0.13187 PDE6A Zornitza Stark Gene: pde6a has been classified as Green List (High Evidence).
Mendeliome v0.13184 PDE4D Zornitza Stark Gene: pde4d has been classified as Green List (High Evidence).
Mendeliome v0.13184 PDE4D Zornitza Stark Phenotypes for gene: PDE4D were changed from to Acrodysostosis 2, with or without hormone resistance, MIM# 614613
Mendeliome v0.13181 PDE4D Zornitza Stark reviewed gene: PDE4D: Rating: GREEN; Mode of pathogenicity: None; Publications: 22464250, 22464252, 23033274, 24203977; Phenotypes: Acrodysostosis 2, with or without hormone resistance, MIM# 614613; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13181 PDE3A Zornitza Stark Gene: pde3a has been classified as Green List (High Evidence).
Mendeliome v0.13181 PDE3A Zornitza Stark Phenotypes for gene: PDE3A were changed from to Hypertension and brachydactyly syndrome - MIM#112410
Mendeliome v0.13179 PDE11A Zornitza Stark Gene: pde11a has been classified as Red List (Low Evidence).
Mendeliome v0.13176 PDE11A Zornitza Stark Classified gene: PDE11A as Red List (low evidence)
Mendeliome v0.13176 PDE11A Zornitza Stark Gene: pde11a has been classified as Red List (Low Evidence).
Mendeliome v0.13175 SHH Zornitza Stark Gene: shh has been classified as Green List (High Evidence).
Mendeliome v0.13175 SHH Zornitza Stark Phenotypes for gene: SHH were changed from to Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250
Mendeliome v0.13172 FAM111B Zornitza Stark reviewed gene: FAM111B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13172 SH3BP2 Zornitza Stark commented on gene: SH3BP2: Cherubism is characterized by a loss of bone, restricted to the jaws, and by the replacement of this bone with fibrous tissues, leading to facial swelling. Involvement of the infraorbital rim and the orbital floor leads to the upward tilting of the eyeballs and consequent exposure of the inferior part of the sclerae, giving a 'cherubic' appearance. Submandibular lymph node enlargement is often reported. Functional impairment includes mastication and speech problems, tooth alterations, and loss of normal vision. Onset of the disease is usually between 14 months and 4 years of age. The disease progresses through puberty, then stabilizes, and in some cases regresses without treatment.
Mendeliome v0.13172 SH3BP2 Zornitza Stark Gene: sh3bp2 has been classified as Green List (High Evidence).
Mendeliome v0.13163 CEBPA Zornitza Stark Classified gene: CEBPA as Green List (high evidence)
Mendeliome v0.13163 CEBPA Zornitza Stark Gene: cebpa has been classified as Green List (High Evidence).
Mendeliome v0.13160 CDKN2A Zornitza Stark Classified gene: CDKN2A as Green List (high evidence)
Mendeliome v0.13160 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Green List (High Evidence).
Mendeliome v0.13159 CDKN1B Zornitza Stark Gene: cdkn1b has been classified as Green List (High Evidence).
Mendeliome v0.13157 SLC12A3 Zornitza Stark Gene: slc12a3 has been classified as Green List (High Evidence).
Mendeliome v0.13153 CC2D2A Zornitza Stark changed review comment from: Multiple families reported with a range of neurological ciliopathies; zebrafish and mouse models.; to: Multiple families reported with a range of neurological ciliopathies; zebrafish and mouse models.

Note single family reported with isolated RP.
Mendeliome v0.13153 PIDD1 Zornitza Stark Phenotypes for gene: PIDD1 were changed from Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum to Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM# 619827
Mendeliome v0.13152 PIDD1 Zornitza Stark edited their review of gene: PIDD1: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM# 619827
Mendeliome v0.13152 SLC12A1 Zornitza Stark Gene: slc12a1 has been classified as Green List (High Evidence).
Mendeliome v0.13149 FGF23 Bryony Thompson Gene: fgf23 has been classified as Green List (High Evidence).
Mendeliome v0.13149 FGF23 Bryony Thompson Phenotypes for gene: FGF23 were changed from to autosomal dominant hypophosphatemic rickets MONDO:0008660; familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome MONDO:0100251
Mendeliome v0.13147 PDX1 Krithika Murali reviewed gene: PDX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9326926, 10545531, 10720084, 12970316, 20009086, 19496967; Phenotypes: Pancreatic agenesis 1 - MIM#260370 (AR), MODY, type IV - MIM#606392(AD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13145 FGF5 Bryony Thompson Phenotypes for gene: FGF5 were changed from Hypertrichosis to hypertrichosis MONDO:0019280
Mendeliome v0.13143 FGF23 Bryony Thompson reviewed gene: FGF23: Rating: GREEN; Mode of pathogenicity: Other; Publications: 11062477, 14966565, 15590700, 16151858, 16030159, 25378588, 34444516; Phenotypes: autosomal dominant hypophosphatemic rickets MONDO:0008660, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome MONDO:0100251; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13141 FGF10 Bryony Thompson Gene: fgf10 has been classified as Green List (High Evidence).
Mendeliome v0.13141 FGF10 Bryony Thompson Phenotypes for gene: FGF10 were changed from to congenital alveolar dysplasia due to FGF10 MONDO:0100090; acinar dysplasia caused by mutation in FGF10 MONDO:0600017
Mendeliome v0.13138 FGF10 Bryony Thompson reviewed gene: FGF10: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916808, 15654336, 16501574, 16630169, 17213838, 33967277, 30639323; Phenotypes: congenital alveolar dysplasia due to FGF10 MONDO:0100090, acinar dysplasia caused by mutation in FGF10 MONDO:0600017; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13138 FFAR4 Bryony Thompson Gene: ffar4 has been classified as Red List (Low Evidence).
Mendeliome v0.13138 FFAR4 Bryony Thompson Phenotypes for gene: FFAR4 were changed from to {Obesity, susceptibility to} MIM#607514
Mendeliome v0.13136 FFAR4 Bryony Thompson Classified gene: FFAR4 as Red List (low evidence)
Mendeliome v0.13136 FFAR4 Bryony Thompson Gene: ffar4 has been classified as Red List (Low Evidence).
Mendeliome v0.13135 FFAR4 Bryony Thompson reviewed gene: FFAR4: Rating: RED; Mode of pathogenicity: None; Publications: 22343897, 34043793; Phenotypes: {Obesity, susceptibility to} MIM#607514; Mode of inheritance: Unknown
Mendeliome v0.13135 FDX2 Bryony Thompson Gene: fdx2 has been classified as Green List (High Evidence).
Mendeliome v0.13132 FDFT1 Bryony Thompson Gene: fdft1 has been classified as Green List (High Evidence).
Mendeliome v0.13129 FBXO7 Bryony Thompson Gene: fbxo7 has been classified as Green List (High Evidence).
Mendeliome v0.13127 FBXW7 Bryony Thompson Phenotypes for gene: FBXW7 were changed from FBXW7-related neurodevelopmental syndrome; Wilms tumour predisposition to neurodevelopmental disorder MONDO:0700092; FBXW7-related neurodevelopmental syndrome; Wilms tumor MONDO:0006058
Mendeliome v0.13125 RSPO1 Belinda Chong reviewed gene: RSPO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17041600, 18085567, 18250098, 18250097; Phenotypes: Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal MIM#610644, Palmoplantar hyperkeratosis and true hermaphroditism MIM#610644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13125 FBP1 Bryony Thompson Gene: fbp1 has been classified as Green List (High Evidence).
Mendeliome v0.13121 FBP1 Bryony Thompson changed review comment from: Well-established gene-disease association. Fructose-1,6-bisphosphatase (FBP1) deficiency is metabolic disorder characterised by episodic acute crises of lactic acidosis and ketotic hypoglycaemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma. Both SNVs and CNVs have been reported.; to: Well-established gene-disease association. Fructose-1,6-bisphosphatase (FBP1) deficiency is a metabolic disorder characterised by episodic acute crises of lactic acidosis and ketotic hypoglycaemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma. Both SNVs and CNVs have been reported.
Mendeliome v0.13120 GLRA2 Zornitza Stark Gene: glra2 has been classified as Green List (High Evidence).
Mendeliome v0.13120 GLRA2 Zornitza Stark Classified gene: GLRA2 as Green List (high evidence)
Mendeliome v0.13120 GLRA2 Zornitza Stark Gene: glra2 has been classified as Green List (High Evidence).
Mendeliome v0.13118 FAT1 Bryony Thompson Phenotypes for gene: FAT1 were changed from facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to syndromic disease MONDO:0002254; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Mendeliome v0.13117 FASTKD2 Bryony Thompson Gene: fastkd2 has been classified as Green List (High Evidence).
Mendeliome v0.13115 FASLG Bryony Thompson Gene: faslg has been classified as Green List (High Evidence).
Mendeliome v0.13112 FAS Bryony Thompson Gene: fas has been classified as Green List (High Evidence).
Mendeliome v0.13109 FARSB Bryony Thompson Gene: farsb has been classified as Green List (High Evidence).
Mendeliome v0.13106 FARS2 Bryony Thompson Gene: fars2 has been classified as Green List (High Evidence).
Mendeliome v0.13103 PDE6H Krithika Murali reviewed gene: PDE6H: Rating: GREEN; Mode of pathogenicity: None; Publications: 22901948; Phenotypes: Achromatopsia 6 - MIM#610024; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13103 FAM58A Bryony Thompson Gene: fam58a has been classified as Green List (High Evidence).
Mendeliome v0.13100 FAM161A Bryony Thompson Gene: fam161a has been classified as Green List (High Evidence).
Mendeliome v0.13100 PDE4D Krithika Murali reviewed gene: PDE4D: Rating: GREEN; Mode of pathogenicity: None; Publications: 24203977, 22464250; Phenotypes: Acrodysostosis 2, with or without hormone resistance-MIM#614613; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13100 PDE3A Krithika Murali reviewed gene: PDE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertension and brachydactyly syndrome - MIM#112410; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13097 FAM126A Bryony Thompson Gene: fam126a has been classified as Green List (High Evidence).
Mendeliome v0.13096 SHH Samantha Ayres reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: 21976454, 12503095, 22791840, 19057928, 19533790; Phenotypes: Holoprosencephaly 3, MIM#142945, Microphthalmia with coloboma 5, MIM#611638, Schizencephaly, MIM#269160, Single median maxillary central incisor, MIM#147250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13094 FAM111B Bryony Thompson Gene: fam111b has been classified as Green List (High Evidence).
Mendeliome v0.13094 FAM111B Bryony Thompson Phenotypes for gene: FAM111B were changed from to hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310
Mendeliome v0.13090 FAM111B Bryony Thompson reviewed gene: FAM111B: Rating: ; Mode of pathogenicity: Other; Publications: 24268661, 26471370, 26495788, 27406236; Phenotypes: hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13090 FAM111A Bryony Thompson Gene: fam111a has been classified as Green List (High Evidence).
Mendeliome v0.13086 FADD Bryony Thompson Gene: fadd has been classified as Green List (High Evidence).
Mendeliome v0.13085 FAH Bryony Thompson Gene: fah has been classified as Green List (High Evidence).
Mendeliome v0.13084 FAH Bryony Thompson Phenotypes for gene: FAH were changed from to Tyrosinemia type I MONDO:0010161
Mendeliome v0.13081 FAH Bryony Thompson reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: None; Publications: 8253378, 1401056, 8364576, 8318997, 25681080; Phenotypes: Tyrosinemia type I MONDO:0010161; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13080 F12 Bryony Thompson Gene: f12 has been classified as Green List (High Evidence).
Mendeliome v0.13078 POMP Zornitza Stark Gene: pomp has been classified as Green List (High Evidence).
Mendeliome v0.13078 POMP Zornitza Stark Phenotypes for gene: POMP were changed from to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma MIM#601952; Proteasome-associated autoinflammatory syndrome 2, MIM# 618048
Mendeliome v0.13075 POMP Zornitza Stark reviewed gene: POMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20226437, 27503413, 29805043; Phenotypes: Keratosis linearis with ichthyosis congenita and sclerosing keratoderma MIM#601952, Proteasome-associated autoinflammatory syndrome 2, MIM# 618048; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13075 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Mendeliome v0.13073 POMT2 Zornitza Stark Gene: pomt2 has been classified as Green List (High Evidence).
Mendeliome v0.13071 PPARA Zornitza Stark Gene: ppara has been classified as Red List (Low Evidence).
Mendeliome v0.13069 PPARA Zornitza Stark Classified gene: PPARA as Red List (low evidence)
Mendeliome v0.13069 PPARA Zornitza Stark Gene: ppara has been classified as Red List (Low Evidence).
Mendeliome v0.13068 PPM1K Zornitza Stark Gene: ppm1k has been classified as Red List (Low Evidence).
Mendeliome v0.13065 PPM1K Zornitza Stark Classified gene: PPM1K as Red List (low evidence)
Mendeliome v0.13065 PPM1K Zornitza Stark Gene: ppm1k has been classified as Red List (Low Evidence).
Mendeliome v0.13064 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
Mendeliome v0.13061 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13061 SGCG Samantha Ayres reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 18285821, 8923014, 7481775, 8968757, 27708273; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13061 CFHR5 Ain Roesley Gene: cfhr5 has been classified as Green List (High Evidence).
Mendeliome v0.13059 CFH Ain Roesley Gene: cfh has been classified as Green List (High Evidence).
Mendeliome v0.13055 PPP1R15B Zornitza Stark Classified gene: PPP1R15B as Amber List (moderate evidence)
Mendeliome v0.13055 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13054 PPP1R3A Zornitza Stark Gene: ppp1r3a has been classified as Red List (Low Evidence).
Mendeliome v0.13054 PPP1R3A Zornitza Stark Phenotypes for gene: PPP1R3A were changed from to Insulin resistance, severe, digenic 125853
Mendeliome v0.13051 PPP1R3A Zornitza Stark Classified gene: PPP1R3A as Red List (low evidence)
Mendeliome v0.13051 PPP1R3A Zornitza Stark Gene: ppp1r3a has been classified as Red List (Low Evidence).
Mendeliome v0.13050 PPP1R3A Zornitza Stark reviewed gene: PPP1R3A: Rating: RED; Mode of pathogenicity: None; Publications: 29948331, 12118251, 18232732; Phenotypes: Insulin resistance, severe, digenic 125853; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13050 PRCD Zornitza Stark Gene: prcd has been classified as Green List (High Evidence).
Mendeliome v0.13047 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13044 PRDM16 Zornitza Stark Classified gene: PRDM16 as Amber List (moderate evidence)
Mendeliome v0.13044 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13043 CFD Ain Roesley Gene: cfd has been classified as Green List (High Evidence).
Mendeliome v0.13040 CEP78 Ain Roesley Gene: cep78 has been classified as Green List (High Evidence).
Mendeliome v0.13038 CEBPA Ain Roesley Gene: cebpa has been classified as Red List (Low Evidence).
Mendeliome v0.13038 CEBPA Ain Roesley Classified gene: CEBPA as Red List (low evidence)
Mendeliome v0.13038 CEBPA Ain Roesley Gene: cebpa has been classified as Red List (Low Evidence).
Mendeliome v0.13037 CEACAM16 Ain Roesley Gene: ceacam16 has been classified as Green List (High Evidence).
Mendeliome v0.13037 CEACAM16 Ain Roesley Phenotypes for gene: CEACAM16 were changed from to Deafness, autosomal dominant 4B, MIM# 614614; Deafness, autosomal recessive 113, MIM# 618410
Mendeliome v0.13036 CEACAM16 Ain Roesley reviewed gene: CEACAM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 21368133, 22544735, 29703829, 25589040, 31249509, 30514912; Phenotypes: Deafness, autosomal dominant 4B, MIM# 614614, Deafness, autosomal recessive 113, MIM# 618410; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13036 CDKN2A Ain Roesley Gene: cdkn2a has been classified as Red List (Low Evidence).
Mendeliome v0.13036 CDKN2A Ain Roesley Classified gene: CDKN2A as Red List (low evidence)
Mendeliome v0.13036 CDKN2A Ain Roesley Gene: cdkn2a has been classified as Red List (Low Evidence).
Mendeliome v0.13035 CDKN1B Ain Roesley Phenotypes for gene: CDKN1B were changed from to Multiple endocrine neoplasia type 4, MEN4, OMIM #610755
Mendeliome v0.13033 CDKN1B Ain Roesley reviewed gene: CDKN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 24819502, 17030811, 23555276; Phenotypes: Multiple endocrine neoplasia type 4, MEN4, OMIM #610755; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13033 CDK4 Ain Roesley Gene: cdk4 has been classified as Red List (Low Evidence).
Mendeliome v0.13032 CDK4 Ain Roesley Classified gene: CDK4 as Red List (low evidence)
Mendeliome v0.13032 CDK4 Ain Roesley Gene: cdk4 has been classified as Red List (Low Evidence).
Mendeliome v0.13031 CDK10 Ain Roesley Gene: cdk10 has been classified as Green List (High Evidence).
Mendeliome v0.13031 CDK10 Ain Roesley Phenotypes for gene: CDK10 were changed from to Al Kaissi syndrome MIM#617694
Mendeliome v0.13030 CDK10 Ain Roesley reviewed gene: CDK10: Rating: GREEN; Mode of pathogenicity: None; Publications: 28886341, 34974531; Phenotypes: Al Kaissi syndrome MIM#617694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13030 CDHR1 Ain Roesley Gene: cdhr1 has been classified as Green List (High Evidence).
Mendeliome v0.13028 CDC73 Ain Roesley Gene: cdc73 has been classified as Green List (High Evidence).
Mendeliome v0.13025 CDC42 Ain Roesley Gene: cdc42 has been classified as Green List (High Evidence).
Mendeliome v0.13024 CDC14A Ain Roesley Gene: cdc14a has been classified as Green List (High Evidence).
Mendeliome v0.13024 CDC14A Ain Roesley Phenotypes for gene: CDC14A were changed from to Deafness, autosomal recessive 32, with or without immotile sperm, MIM# 608653
Mendeliome v0.13022 CDC14A Ain Roesley reviewed gene: CDC14A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29293958, 2725905; Phenotypes: Deafness, autosomal recessive 32, with or without immotile sperm, MIM# 608653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13022 CD79B Ain Roesley Gene: cd79b has been classified as Green List (High Evidence).
Mendeliome v0.13020 PRDM5 Zornitza Stark Gene: prdm5 has been classified as Green List (High Evidence).
Mendeliome v0.13017 PREPL Zornitza Stark Gene: prepl has been classified as Green List (High Evidence).
Mendeliome v0.13014 PRG4 Zornitza Stark Gene: prg4 has been classified as Green List (High Evidence).
Mendeliome v0.13010 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Green List (High Evidence).
Mendeliome v0.13010 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from to Epilepsy, progressive myoclonic 1B, MIM# 612437
Mendeliome v0.13007 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34597683, 30564977, 30345727, 29790814, 26727662, 31035234; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13007 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Mendeliome v0.13007 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from to Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489
Mendeliome v0.13004 PRKAR1A Zornitza Stark reviewed gene: PRKAR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 10973256, 11115848, 12424709, 21651393; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM# 101800, Carney complex, type 1, MIM# 160980, Myxoma, intracardiac, MIM# 255960, Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13004 PRKCG Zornitza Stark Gene: prkcg has been classified as Green List (High Evidence).
Mendeliome v0.13001 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Green List (High Evidence).
Mendeliome v0.12998 PRMT7 Zornitza Stark Gene: prmt7 has been classified as Green List (High Evidence).
Mendeliome v0.12995 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Mendeliome v0.12992 PROK2 Zornitza Stark Gene: prok2 has been classified as Green List (High Evidence).
Mendeliome v0.12989 PROM1 Zornitza Stark Gene: prom1 has been classified as Green List (High Evidence).
Mendeliome v0.12986 PROS1 Zornitza Stark Gene: pros1 has been classified as Green List (High Evidence).
Mendeliome v0.12986 PROS1 Zornitza Stark Phenotypes for gene: PROS1 were changed from to Thrombophilia 5 due to protein S deficiency, autosomal dominant, MIM# 612336; Thrombophilia 5 due to protein S deficiency, autosomal recessive, MIM# 614514
Mendeliome v0.12983 PROS1 Zornitza Stark reviewed gene: PROS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7545463, 19466456, 10063989, 20484936, 19729839; Phenotypes: Thrombophilia 5 due to protein S deficiency, autosomal dominant, MIM# 612336, Thrombophilia 5 due to protein S deficiency, autosomal recessive, MIM# 614514; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12983 PRPF3 Zornitza Stark Gene: prpf3 has been classified as Green List (High Evidence).
Mendeliome v0.12980 PRPF4 Zornitza Stark Gene: prpf4 has been classified as Green List (High Evidence).
Mendeliome v0.12977 PRPF6 Zornitza Stark Gene: prpf6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12974 PRPF6 Zornitza Stark Classified gene: PRPF6 as Amber List (moderate evidence)
Mendeliome v0.12974 PRPF6 Zornitza Stark Gene: prpf6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12973 PRPH Zornitza Stark Gene: prph has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12973 PRPH Zornitza Stark Phenotypes for gene: PRPH were changed from to {Amyotrophic lateral sclerosis, susceptibility to}, 105400
Mendeliome v0.12970 PRPH Zornitza Stark Classified gene: PRPH as Amber List (moderate evidence)
Mendeliome v0.12970 PRPH Zornitza Stark Gene: prph has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12969 PRPH Zornitza Stark reviewed gene: PRPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 20363051, 15322088, 15446584; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to}, 105400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12969 PRSS1 Zornitza Stark Gene: prss1 has been classified as Green List (High Evidence).
Mendeliome v0.12966 PRSS12 Zornitza Stark Gene: prss12 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12963 PRSS12 Zornitza Stark Classified gene: PRSS12 as Amber List (moderate evidence)
Mendeliome v0.12963 PRSS12 Zornitza Stark Gene: prss12 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12962 PSMC2 Zornitza Stark Gene: psmc2 has been classified as Red List (Low Evidence).
Mendeliome v0.12962 PSMC2 Zornitza Stark Classified gene: PSMC2 as Red List (low evidence)
Mendeliome v0.12962 PSMC2 Zornitza Stark Gene: psmc2 has been classified as Red List (Low Evidence).
Mendeliome v0.12961 PSMC3IP Zornitza Stark Gene: psmc3ip has been classified as Green List (High Evidence).
Mendeliome v0.12961 PSMC3IP Zornitza Stark Phenotypes for gene: PSMC3IP were changed from to Ovarian dysgenesis 3, MIM# 614324
Mendeliome v0.12958 PSMC3IP Zornitza Stark reviewed gene: PSMC3IP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21963259, 35352317, 34878148, 30406445, 29240891; Phenotypes: Ovarian dysgenesis 3, MIM# 614324; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12958 PSMD12 Zornitza Stark Gene: psmd12 has been classified as Green List (High Evidence).
Mendeliome v0.12958 PSMD12 Zornitza Stark Phenotypes for gene: PSMD12 were changed from to Stankiewicz-Isidor syndrome, MIM# 617516
Mendeliome v0.12955 PSMD12 Zornitza Stark reviewed gene: PSMD12: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132691, 34906456; Phenotypes: Stankiewicz-Isidor syndrome, MIM# 617516; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12955 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Mendeliome v0.12952 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
Mendeliome v0.12949 PTGDR Zornitza Stark Gene: ptgdr has been classified as Red List (Low Evidence).
Mendeliome v0.12947 PTGDR Zornitza Stark Classified gene: PTGDR as Red List (low evidence)
Mendeliome v0.12947 PTGDR Zornitza Stark Gene: ptgdr has been classified as Red List (Low Evidence).
Mendeliome v0.12946 PTH Zornitza Stark Gene: pth has been classified as Green List (High Evidence).
Mendeliome v0.12943 PTH1R Zornitza Stark Gene: pth1r has been classified as Green List (High Evidence).
Mendeliome v0.12943 PTH1R Zornitza Stark Phenotypes for gene: PTH1R were changed from to Failure of tooth eruption, primary MIM#125350; Eiken syndrome MIM#600002; Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400; Chondrodysplasia, Blomstrand type MIM#215045
Mendeliome v0.12940 PTH1R Zornitza Stark reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Failure of tooth eruption, primary MIM#125350, Eiken syndrome MIM#600002, Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400, Chondrodysplasia, Blomstrand type MIM#215045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12940 PTHLH Zornitza Stark Gene: pthlh has been classified as Green List (High Evidence).
Mendeliome v0.12937 PTPN14 Zornitza Stark Gene: ptpn14 has been classified as Green List (High Evidence).
Mendeliome v0.12937 PTPN14 Zornitza Stark Phenotypes for gene: PTPN14 were changed from to Choanal atresia and lymphoedema, MIM# 613611
Mendeliome v0.12934 PTPN14 Zornitza Stark reviewed gene: PTPN14: Rating: GREEN; Mode of pathogenicity: None; Publications: 20826270; Phenotypes: Choanal atresia and lymphoedema, MIM# 613611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12932 TCF3 Zornitza Stark Phenotypes for gene: TCF3 were changed from Agammaglobulinaemia 8, autosomal dominant, MIM# 616941 to Agammaglobulinaemia 8, autosomal dominant, MIM# 616941; Agammaglobulinaemia 8B, autosomal recessive, MIM# 619824
Mendeliome v0.12931 TCF3 Zornitza Stark edited their review of gene: TCF3: Changed phenotypes: Agammaglobulinaemia 8, autosomal dominant, MIM# 616941, Agammaglobulinaemia 8B, autosomal recessive, MIM# 619824
Mendeliome v0.12930 PTPN22 Zornitza Stark Gene: ptpn22 has been classified as Red List (Low Evidence).
Mendeliome v0.12929 PTPN22 Zornitza Stark Classified gene: PTPN22 as Red List (low evidence)
Mendeliome v0.12929 PTPN22 Zornitza Stark Gene: ptpn22 has been classified as Red List (Low Evidence).
Mendeliome v0.12928 PTPRO Zornitza Stark Gene: ptpro has been classified as Green List (High Evidence).
Mendeliome v0.12925 PTRH2 Zornitza Stark Gene: ptrh2 has been classified as Green List (High Evidence).
Mendeliome v0.12922 PTRH2 Zornitza Stark commented on gene: PTRH2: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease-1 (IMNEPD1) is an autosomal recessive multisystemic disorder with variable expressivity. The core features usually include global developmental delay with impaired intellectual development and speech delay, ataxia, sensorineural hearing loss, and pancreatic insufficiency. Additional features may include peripheral neuropathy, postnatal microcephaly, dysmorphic facial features, and cerebellar atrophy.

More than 5 unrelated families reported. The Q85P missense variant is reported in several families, likely founder effect.
Mendeliome v0.12922 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Mendeliome v0.12920 PUM1 Zornitza Stark Gene: pum1 has been classified as Green List (High Evidence).
Mendeliome v0.12917 PYCR2 Zornitza Stark Gene: pycr2 has been classified as Green List (High Evidence).
Mendeliome v0.12913 PYROXD1 Zornitza Stark Gene: pyroxd1 has been classified as Green List (High Evidence).
Mendeliome v0.12910 F12 Bryony Thompson commented on gene: F12: Also associated with FXII deficiency - PMID: 29383625, 20022356, 18024408, 20386432, 26709783, 21264442, 28007010, 15205584, 30700128 - Biallalelic loss-of-function variants are a well-established cause of FXII deficiency. FXII deficiency is not associated with bleeding risk unlike other coagulation factors, it is either asymptomatic or characterized by a prolonged activated partial thromboplastin time. DEFINITIVE gene-disease validity classification by the ClinGen Hemostasis Thrombosis VCEP, Classification - 01/22/2020
Mendeliome v0.12910 SGCD Zornitza Stark Gene: sgcd has been classified as Green List (High Evidence).
Mendeliome v0.12910 SGCD Zornitza Stark Phenotypes for gene: SGCD were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287; autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Mendeliome v0.12907 SGCD Zornitza Stark reviewed gene: SGCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841194, 19259135, 20623375, 10838250, 10735275, 9832045, 30733730; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12907 SGCB Zornitza Stark Gene: sgcb has been classified as Green List (High Evidence).
Mendeliome v0.12907 SGCB Zornitza Stark Phenotypes for gene: SGCB were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286; autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152
Mendeliome v0.12904 SGCA Zornitza Stark Gene: sgca has been classified as Green List (High Evidence).
Mendeliome v0.12904 SGCA Zornitza Stark Phenotypes for gene: SGCA were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099; autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152
Mendeliome v0.12901 SFXN4 Zornitza Stark Gene: sfxn4 has been classified as Green List (High Evidence).
Mendeliome v0.12898 SFRP4 Zornitza Stark Gene: sfrp4 has been classified as Green List (High Evidence).
Mendeliome v0.12895 RASGRP1 Zornitza Stark Gene: rasgrp1 has been classified as Green List (High Evidence).
Mendeliome v0.12892 PDCD1 Zornitza Stark Gene: pdcd1 has been classified as Red List (Low Evidence).
Mendeliome v0.12888 PDCD1 Zornitza Stark Classified gene: PDCD1 as Red List (low evidence)
Mendeliome v0.12888 PDCD1 Zornitza Stark Gene: pdcd1 has been classified as Red List (Low Evidence).
Mendeliome v0.12887 PCK2 Zornitza Stark Gene: pck2 has been classified as Red List (Low Evidence).
Mendeliome v0.12885 PCK2 Zornitza Stark Classified gene: PCK2 as Red List (low evidence)
Mendeliome v0.12885 PCK2 Zornitza Stark Gene: pck2 has been classified as Red List (Low Evidence).
Mendeliome v0.12883 PCCB Zornitza Stark Gene: pccb has been classified as Green List (High Evidence).
Mendeliome v0.12880 PCCA Zornitza Stark Gene: pcca has been classified as Green List (High Evidence).
Mendeliome v0.12877 FXR1 Bryony Thompson Phenotypes for gene: FXR1 were changed from Congenital multi-minicore myopathy; multiminicore myopathy MONDO:0018948 to Congenital multi-minicore myopathy; myopathy, congenital proximal, with minicore lesions MONDO:0032937
Mendeliome v0.12874 PC Zornitza Stark Gene: pc has been classified as Green List (High Evidence).
Mendeliome v0.12871 PAX9 Zornitza Stark Gene: pax9 has been classified as Green List (High Evidence).
Mendeliome v0.12871 PAX9 Zornitza Stark Phenotypes for gene: PAX9 were changed from to Tooth agenesis, selective, 3 - MIM#604625
Mendeliome v0.12866 SET Zornitza Stark Gene: set has been classified as Green List (High Evidence).
Mendeliome v0.12863 SERPING1 Zornitza Stark Gene: serping1 has been classified as Green List (High Evidence).
Mendeliome v0.12859 SGCD Samantha Ayres reviewed gene: SGCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841194, 30733730, 10838250; Phenotypes: autosomal recessive limb-girdle muscular dystrophy MONDO:0015152, Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM#601287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SGCB Samantha Ayres reviewed gene: SGCB: Rating: GREEN; Mode of pathogenicity: None; Publications: 18285821; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286, autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SGCA Samantha Ayres reviewed gene: SGCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 30007747, 9192266, 34404573; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099, autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SERPIND1 Zornitza Stark Gene: serpind1 has been classified as Green List (High Evidence).
Mendeliome v0.12855 PDCD1 Krithika Murali changed review comment from: No OMIM gene disease association.

1 individual from a consanguineous family reported with PDCD1 deficiency.

PMID: 34183838 (Nat Medicine 2021) - proband is the son of consanguineous Turkish parents. He was diagnosed with type 1 diabetes (T1D), hypothyroidism, and juvenile idiopathic arthritis (JIA) at the age of three years. He developed abdominal TB age 10 and died from pulmonary alveolar haemorrhage age 11. WES identified homozygous intragenic PDCD1 gene duplication (c.105dupC p.T36Hfs*70). Absent from population databases and unaffected parents confirmed to be heterozygous. Supportive in vitro studies showing absent expression or function of PD-1 protein. Proband's older brother died at the age of 3 from unexplained pneumonitis and had a history of T1DM and juvenile idiopathic arthritis.; to: No OMIM gene disease association.

1 individual from a consanguineous family reported with PDCD1 deficiency.

PMID: 34183838 (Nat Medicine 2021) - proband is the son of consanguineous Turkish parents. He was diagnosed with type 1 diabetes (T1D), hypothyroidism, and juvenile idiopathic arthritis (JIA) at the age of three years. He developed abdominal TB age 10 and died from pulmonary alveolar haemorrhage age 11. WES identified homozygous intragenic PDCD1 gene duplication (c.105dupC p.T36Hfs*70). Absent from population databases and unaffected parents confirmed to be heterozygous. Supportive in vitro studies showing absent expression or function of PD-1 protein. Proband's older brother died at the age of 3 from unexplained pneumonitis and had a history of T1DM and juvenile idiopathic arthritis.
Mendeliome v0.12855 CD79A Ain Roesley Gene: cd79a has been classified as Green List (High Evidence).
Mendeliome v0.12853 CD70 Ain Roesley Gene: cd70 has been classified as Green List (High Evidence).
Mendeliome v0.12851 CD55 Ain Roesley Gene: cd55 has been classified as Green List (High Evidence).
Mendeliome v0.12851 CD55 Ain Roesley Phenotypes for gene: CD55 were changed from to Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300
Mendeliome v0.12849 CD55 Ain Roesley reviewed gene: CD55: Rating: GREEN; Mode of pathogenicity: None; Publications: 28657829, 28657861; Phenotypes: Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12849 CD46 Ain Roesley Gene: cd46 has been classified as Green List (High Evidence).
Mendeliome v0.12848 CD40 Ain Roesley Gene: cd40 has been classified as Green List (High Evidence).
Mendeliome v0.12846 CD36 Ain Roesley Gene: cd36 has been classified as Green List (High Evidence).
Mendeliome v0.12844 CD209 Ain Roesley Gene: cd209 has been classified as Red List (Low Evidence).
Mendeliome v0.12844 CD209 Ain Roesley Phenotypes for gene: CD209 were changed from to {Dengue fever, protection against} MIM#614371; {HIV type 1, susceptibility to} MIM#609423; {Mycobacterium tuberculosis, susceptibility to} MIM#607948
Mendeliome v0.12844 CD209 Ain Roesley Classified gene: CD209 as Red List (low evidence)
Mendeliome v0.12844 CD209 Ain Roesley Gene: cd209 has been classified as Red List (Low Evidence).
Mendeliome v0.12843 CD209 Ain Roesley reviewed gene: CD209: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Dengue fever, protection against} MIM#614371, {HIV type 1, susceptibility to} MIM#609423, {Mycobacterium tuberculosis, susceptibility to} MIM#607948; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.12843 CD151 Ain Roesley Gene: cd151 has been classified as Green List (High Evidence).
Mendeliome v0.12843 CD151 Ain Roesley Phenotypes for gene: CD151 were changed from to Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057
Mendeliome v0.12841 CD151 Ain Roesley reviewed gene: CD151: Rating: GREEN; Mode of pathogenicity: None; Publications: 15265795, 29138120; Phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12841 CCR5 Ain Roesley Gene: ccr5 has been classified as Green List (High Evidence).
Mendeliome v0.12841 CCR5 Ain Roesley Phenotypes for gene: CCR5 were changed from to {Hepatitis C virus, resistance to} 609532; {HIV infection, susceptibility/resistance to}; {West nile virus, susceptibility to}MIM# 610379
Mendeliome v0.12839 CCR5 Ain Roesley reviewed gene: CCR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hepatitis C virus, resistance to} 609532, {HIV infection, susceptibility/resistance to}, {West nile virus, susceptibility to}MIM# 610379; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12839 CCR2 Ain Roesley Phenotypes for gene: CCR2 were changed from to {HIV infection, susceptibility/resistance to}
Mendeliome v0.12838 CCR2 Ain Roesley changed review comment from: Currently no mendelian gene-disease association; to: Vall64Ile has been associated with reduction in the progression to AIDS. Mutant results in normal expression levels of the CCR2 receptor and has no effect on the incidence of HIV infection. However, in contrast to normal CCR2 peptides, the mutant protein preferentially dimerizes with the CXCR4 polypeptide, isolating it in the endoplasmic reticulum. It is also thought that the inhibitory effect is dependent on the stages of HIV-1 infection and interactions with other genetic variants.
Mendeliome v0.12838 CCR2 Ain Roesley edited their review of gene: CCR2: Changed phenotypes: {HIV infection, susceptibility/resistance to}
Mendeliome v0.12838 CCR2 Ain Roesley Classified gene: CCR2 as Red List (low evidence)
Mendeliome v0.12838 CCR2 Ain Roesley Gene: ccr2 has been classified as Red List (Low Evidence).
Mendeliome v0.12837 CCR2 Ain Roesley Classified gene: CCR2 as Red List (low evidence)
Mendeliome v0.12837 CCR2 Ain Roesley Gene: ccr2 has been classified as Red List (Low Evidence).
Mendeliome v0.12836 CCR2 Ain Roesley Gene: ccr2 has been classified as Green List (High Evidence).
Mendeliome v0.12836 SLC25A12 Zornitza Stark Gene: slc25a12 has been classified as Green List (High Evidence).
Mendeliome v0.12833 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Mendeliome v0.12830 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Mendeliome v0.12827 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Green List (High Evidence).
Mendeliome v0.12827 SLC25A19 Zornitza Stark Phenotypes for gene: SLC25A19 were changed from to Microcephaly, Amish type, MIM#607196; Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710
Mendeliome v0.12824 SLC25A19 Zornitza Stark reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: None; Publications: 31506564, 31295743, 12185364, 19798730; Phenotypes: Microcephaly, Amish type, MIM#607196, Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12824 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Mendeliome v0.12821 TRPM1 Zornitza Stark Gene: trpm1 has been classified as Green List (High Evidence).
Mendeliome v0.12821 TRPM1 Zornitza Stark Phenotypes for gene: TRPM1 were changed from to Night blindness, congenital stationary (complete), 1C, autosomal recessive, MIM# 613216
Mendeliome v0.12818 TRPM1 Zornitza Stark reviewed gene: TRPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19878917, 19896113, 19896109; Phenotypes: Night blindness, congenital stationary (complete), 1C, autosomal recessive, MIM# 613216; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12818 TRPC6 Zornitza Stark Gene: trpc6 has been classified as Green List (High Evidence).
Mendeliome v0.12818 TRPC6 Zornitza Stark Phenotypes for gene: TRPC6 were changed from to Glomerulosclerosis, focal segmental, 2, MIM# 603965
Mendeliome v0.12815 TRPC6 Zornitza Stark reviewed gene: TRPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15879175, 15924139, 34387384, 33918778, 32509715; Phenotypes: Glomerulosclerosis, focal segmental, 2, MIM# 603965; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Gene: trappc2 has been classified as Green List (High Evidence).
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Phenotypes for gene: TRAPPC2 were changed from to Spondyloepiphyseal dysplasia tarda, MIM# 313400
Mendeliome v0.12812 TRAPPC2 Zornitza Stark reviewed gene: TRAPPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10431248, 14755465, 33726005, 20301324, 32953644; Phenotypes: Spondyloepiphyseal dysplasia tarda, MIM# 313400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.12812 TRAPPC12 Zornitza Stark Gene: trappc12 has been classified as Green List (High Evidence).
Mendeliome v0.12812 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Mendeliome v0.12812 TRAPPC11 Zornitza Stark Phenotypes for gene: TRAPPC11 were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 18, MIM# 615356
Mendeliome v0.12809 TRAPPC11 Zornitza Stark reviewed gene: TRAPPC11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23830518, 26322222, 29855340, 30105108; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18, MIM# 615356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12809 TRAK1 Zornitza Stark Gene: trak1 has been classified as Green List (High Evidence).
Mendeliome v0.12806 TPMT Zornitza Stark Gene: tpmt has been classified as Red List (Low Evidence).
Mendeliome v0.12805 TPMT Zornitza Stark Classified gene: TPMT as Red List (low evidence)
Mendeliome v0.12805 TPMT Zornitza Stark Gene: tpmt has been classified as Red List (Low Evidence).
Mendeliome v0.12804 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Green List (High Evidence).
Mendeliome v0.12804 TRNT1 Zornitza Stark Phenotypes for gene: TRNT1 were changed from to Retinitis pigmentosa and erythrocytic microcytosis, MIM# 616959; Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084
Mendeliome v0.12801 TRNT1 Zornitza Stark reviewed gene: TRNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25193871, 23553769, 29170023, 27389523, 26494905; Phenotypes: Retinitis pigmentosa and erythrocytic microcytosis, MIM# 616959, Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12801 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Mendeliome v0.12801 TRMU Zornitza Stark Phenotypes for gene: TRMU were changed from to Liver failure, transient infantile, MIM# 613070
Mendeliome v0.12798 TRMU Zornitza Stark reviewed gene: TRMU: Rating: GREEN; Mode of pathogenicity: None; Publications: 19732863; Phenotypes: Liver failure, transient infantile, MIM# 613070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12798 TRMT5 Zornitza Stark Gene: trmt5 has been classified as Green List (High Evidence).
Mendeliome v0.12793 ETV1 Bryony Thompson Gene: etv1 has been classified as Red List (Low Evidence).
Mendeliome v0.12791 ETV1 Bryony Thompson Classified gene: ETV1 as Red List (low evidence)
Mendeliome v0.12791 ETV1 Bryony Thompson Gene: etv1 has been classified as Red List (Low Evidence).
Mendeliome v0.12790 EXOC3L2 Bryony Thompson Phenotypes for gene: EXOC3L2 were changed from Dandy-Walker malformation; renal dysplasia; bone marrow failure to Dandy-Walker malformation, MONDO:0009072; renal dysplasia; bone marrow failure
Mendeliome v0.12789 ETFDH Bryony Thompson Gene: etfdh has been classified as Green List (High Evidence).
Mendeliome v0.12787 TRMT10C Zornitza Stark Gene: trmt10c has been classified as Green List (High Evidence).
Mendeliome v0.12784 PDHA2 Zornitza Stark Gene: pdha2 has been classified as Red List (Low Evidence).
Mendeliome v0.12783 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Mendeliome v0.12780 TRHR Zornitza Stark Gene: trhr has been classified as Green List (High Evidence).
Mendeliome v0.12777 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Mendeliome v0.12774 TRIM32 Zornitza Stark Gene: trim32 has been classified as Green List (High Evidence).
Mendeliome v0.12774 TRIM32 Zornitza Stark Phenotypes for gene: TRIM32 were changed from to Bardet-Biedl syndrome 11, MIM# 615988; Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
Mendeliome v0.12771 TRIM32 Zornitza Stark changed review comment from: Single family reported in 2006.; to: BBS: Single family reported in 2006. LIMITED.
Mendeliome v0.12771 TRIM32 Zornitza Stark edited their review of gene: TRIM32: Added comment: >3 unrelated cases with myopathy, adult onset reported; Changed rating: GREEN; Changed publications: 16606853, 31309175, 11822024; Changed phenotypes: Bardet-Biedl syndrome 11, MIM# 615988, Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
Mendeliome v0.12771 TRPM4 Zornitza Stark Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12771 TRPM4 Zornitza Stark Phenotypes for gene: TRPM4 were changed from to Progressive familial heart block, type IB, MIM# 604559; Erythrokeratodermia variabilis et progressiva 6, MIM# 618531
Mendeliome v0.12768 TRPM4 Zornitza Stark Classified gene: TRPM4 as Amber List (moderate evidence)
Mendeliome v0.12768 TRPM4 Zornitza Stark Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12767 TRPM4 Zornitza Stark reviewed gene: TRPM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 19726882, 20562447, 21887725, 20562447, 35205305, 34897640, 30528822; Phenotypes: Progressive familial heart block, type IB, MIM# 604559, Erythrokeratodermia variabilis et progressiva 6 618531; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12767 TRPV4 Zornitza Stark Gene: trpv4 has been classified as Green List (High Evidence).
Mendeliome v0.12765 TTPA Zornitza Stark Gene: ttpa has been classified as Green List (High Evidence).
Mendeliome v0.12762 TTC19 Zornitza Stark Gene: ttc19 has been classified as Green List (High Evidence).
Mendeliome v0.12759 TTC19 Zornitza Stark edited their review of gene: TTC19: Added comment: Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life. The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances.

At least 4 unrelated families reported.; Changed publications: 21278747, 23532514, 24368687, 24397319
Mendeliome v0.12759 TSFM Zornitza Stark Gene: tsfm has been classified as Green List (High Evidence).
Mendeliome v0.12756 PAX9 Krithika Murali reviewed gene: PAX9: Rating: GREEN; Mode of pathogenicity: None; Publications: 10615120, 16479262; Phenotypes: Tooth agenesis, selective, 3 - MIM#604625; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12756 TPK1 Zornitza Stark Gene: tpk1 has been classified as Green List (High Evidence).
Mendeliome v0.12753 TP63 Zornitza Stark Gene: tp63 has been classified as Green List (High Evidence).
Mendeliome v0.12753 TP63 Zornitza Stark Phenotypes for gene: TP63 were changed from to ADULT syndrome, OMIM #103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292; Hay-Wells syndrome, OMIM #106260; Limb-mammary syndrome, OMIM #603543; Orofacial cleft 8, OMIM #618149; Rapp-Hodgkin syndrome, OMIM #129400; Split-hand/foot malformation 4, OMIM #605289
Mendeliome v0.12750 TP63 Zornitza Stark reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: None; Publications: 20556892; Phenotypes: ADULT syndrome, OMIM #103285, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292, Hay-Wells syndrome, OMIM #106260, Limb-mammary syndrome, OMIM #603543, Orofacial cleft 8, OMIM #618149, Rapp-Hodgkin syndrome, OMIM #129400, Split-hand/foot malformation 4, OMIM #605289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12750 TOR1A Zornitza Stark Gene: tor1a has been classified as Green List (High Evidence).
Mendeliome v0.12750 TOR1A Zornitza Stark Phenotypes for gene: TOR1A were changed from to Arthrogryposis multiplex congenita, MIM#618947; Dystonia-1, torsion, MIM#128100
Mendeliome v0.12747 TOR1A Zornitza Stark reviewed gene: TOR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30244176, 9288096, 19955557, 18477710, 32243914, 31583275, 31347572; Phenotypes: Arthrogryposis multiplex congenita, MIM#618947, Dystonia-1, torsion, MIM#128100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12747 TNXB Zornitza Stark Gene: tnxb has been classified as Green List (High Evidence).
Mendeliome v0.12747 TNXB Zornitza Stark Phenotypes for gene: TNXB were changed from to Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408
Mendeliome v0.12744 TNXB Zornitza Stark reviewed gene: TNXB: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306229, 28306225, 23620400; Phenotypes: Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12744 TNPO3 Zornitza Stark Gene: tnpo3 has been classified as Green List (High Evidence).
Mendeliome v0.12741 RSPO2 Zornitza Stark Gene: rspo2 has been classified as Green List (High Evidence).
Mendeliome v0.12738 PIGA Zornitza Stark changed review comment from: PIGA 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.; to: PMID 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.
Mendeliome v0.12738 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466; Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072
Mendeliome v0.12737 PIGA Zornitza Stark edited their review of gene: PIGA: Added comment: PIGA 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.; Changed publications: 22305531, 24357517, 24706016, 26545172, 33333793, 32694024, 34875027; Changed phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466, Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072
Mendeliome v0.12737 SLC35B2 Zornitza Stark Phenotypes for gene: SLC35B2 were changed from chondrodysplasia with hypomyelinating leukodystrophy, intellectual disability to Leukodystrophy, MONDO:0019046, SLC35B2-related
Mendeliome v0.12733 TNNC1 Zornitza Stark Gene: tnnc1 has been classified as Green List (High Evidence).
Mendeliome v0.12733 CACNA2D1 Alison Yeung Gene: cacna2d1 has been classified as Green List (High Evidence).
Mendeliome v0.12732 CACNA2D1 Alison Yeung Classified gene: CACNA2D1 as Green List (high evidence)
Mendeliome v0.12732 CACNA2D1 Alison Yeung Gene: cacna2d1 has been classified as Green List (High Evidence).
Mendeliome v0.12731 CACNA2D1 Michelle Torres gene: CACNA2D1 was added
gene: CACNA2D1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CACNA2D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA2D1 were set to 35293990
Phenotypes for gene: CACNA2D1 were set to developmental and epileptic encephalopathy disorder MONDO:0100062 CACNA2D1-related
Review for gene: CACNA2D1 was set to GREEN
Added comment: PMID 35293990: WES of 2x unrelated individuals with early-onset developmental epileptic encephalopathy, microcephaly, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia, and 2 cortical visual impairment, corpus callosum hypoplasia and progressive volume loss. Patient 2 also had a tiny patent foramen ovale.

Patient 1 is homozygous for p.(Ser275Asnfs*13). mRNA and protein expression were reduced to ~10% of WT in fibroblasts

Patient 2 is cHet for p.(Leu9Alafs*5) and p.(Gly209Asp). mRNA expression in patients fibroblasts was similar to controls, and protein expression reduced to 31-38%. Functional of the p.(Gly209Asp) showed impaired localization and mutagenesis showed complete loss of channel function.
Sources: Literature
Mendeliome v0.12731 TRAPPC10 Zornitza Stark Gene: trappc10 has been classified as Green List (High Evidence).
Mendeliome v0.12731 TRAPPC10 Zornitza Stark Classified gene: TRAPPC10 as Green List (high evidence)
Mendeliome v0.12731 TRAPPC10 Zornitza Stark Gene: trappc10 has been classified as Green List (High Evidence).
Mendeliome v0.12729 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome; Glomerular disorder MONDO:0019722, TTC21B-related
Mendeliome v0.12728 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from {Neural tube defects, susceptibility to} MIM#182940 to {Neural tube defects, susceptibility to} MIM#182940; craniosynostosis, FUZ-related MONDO#0015469
Mendeliome v0.12726 FUZ Anna Ritchie reviewed gene: FUZ: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34719684; Phenotypes: craniosynostosis, FUZ-related MONDO#0015469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12726 TNNI1 Zornitza Stark Gene: tnni1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12726 TNNI1 Zornitza Stark Classified gene: TNNI1 as Amber List (moderate evidence)
Mendeliome v0.12726 TNNI1 Zornitza Stark Gene: tnni1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12725 TNNI1 Zornitza Stark Phenotypes for gene: TNNI1 were changed from arthrogryposis; joint contractures to Arthrogryposis MONDO:0008779, TNNI1-related
Mendeliome v0.12724 SLC35B2 Alison Yeung Gene: slc35b2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12724 SLC35B2 Alison Yeung Classified gene: SLC35B2 as Amber List (moderate evidence)
Mendeliome v0.12724 SLC35B2 Alison Yeung Gene: slc35b2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12723 ATP2B1 Zornitza Stark Gene: atp2b1 has been classified as Green List (High Evidence).
Mendeliome v0.12723 ATP2B1 Zornitza Stark Classified gene: ATP2B1 as Green List (high evidence)
Mendeliome v0.12723 ATP2B1 Zornitza Stark Gene: atp2b1 has been classified as Green List (High Evidence).
Mendeliome v0.12722 SLC35B2 Melanie Marty changed review comment from: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature; to: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature
Mendeliome v0.12720 MDFIC Zornitza Stark Gene: mdfic has been classified as Green List (High Evidence).
Mendeliome v0.12720 TTC21B Dean Phelan reviewed gene: TTC21B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35289079; Phenotypes: early onset hypertension, proteinuria, progressive kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12720 FUZ Anna Ritchie changed review comment from: Novel missense p.(Arg284Pro) mutation in FUZ identified in twins presenting with craniosynostosis. Loss of Fuz resulted in increased mineralisation in both in vitro embryonic primary osteoblast cultures and in fibroblasts undergoing an osteogenic challenge. No previous reports have implicated changes in human FUZ in craniosynostosis. However, variations in FUZ have been found in patients with neural tube defects.; to: Novel missense p.(Arg284Pro) mutation in FUZ identified in twins presenting with craniosynostosis. Loss of Fuz resulted in increased mineralisation in both in vitro embryonic primary osteoblast cultures and in fibroblasts undergoing an osteogenic challenge. No previous reports have implicated changes in human FUZ in craniosynostosis. However, variations in FUZ have been found in patients with neural tube defects.
Mendeliome v0.12719 ADAM22 Alison Yeung Classified gene: ADAM22 as Green List (high evidence)
Mendeliome v0.12719 ADAM22 Alison Yeung Gene: adam22 has been classified as Green List (High Evidence).
Mendeliome v0.12717 MDFIC Zornitza Stark Classified gene: MDFIC as Green List (high evidence)
Mendeliome v0.12717 MDFIC Zornitza Stark Gene: mdfic has been classified as Green List (High Evidence).
Mendeliome v0.12716 FUZ Anna Ritchie reviewed gene: FUZ: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34719684; Phenotypes: Craniosynostosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12714 TNNI1 Krithika Murali gene: TNNI1 was added
gene: TNNI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNNI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNI1 were set to 34934811
Phenotypes for gene: TNNI1 were set to arthrogryposis; joint contractures
Review for gene: TNNI1 was set to AMBER
Added comment: No OMIM gene disease association reported

PMID 34934811 Nishimori et al report 2 individuals from a Japanese family with joint contractures, elevated CK and a novel heterozygous TNNI1 variant.

The proband was born with clasped thumbs (gestational age not stated) requiring surgical correction at 5 months of age. At age 14 was diagnosed with contractures of the neck, trunk, hip and knee with elevated serum CK (1689 IU/L). No muscle weakness noted. Muscle biopsy showed moth-eaten appearance of type I fibres and electron microscopy showed type 1 fibre Z disk streaming.

Trio exome sequencing identified a paternally heterozygous nonsense TNNI1 variant (c.523A>T p.K175*). The proband's father and paternal grandfather (not genotyped) also have a history of joint contractures with elevated CK.

The affected amino acid residue is in the tropomyosin binding site near the C-terminus and is highly conserved. The variant is absent from gnomAD. rt-PCR products of mRNA from the patient's muscle biopsy showed presence of both mutated and normal transcripts.
Sources: Literature
Mendeliome v0.12714 SLC35B2 Melanie Marty gene: SLC35B2 was added
gene: SLC35B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC35B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35B2 were set to PMID: 35325049
Phenotypes for gene: SLC35B2 were set to chondrodysplasia with hypomyelinating leukodystrophy, intellectual disability
Review for gene: SLC35B2 was set to AMBER
Added comment: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature
Mendeliome v0.12714 AHSG Elena Savva gene: AHSG was added
gene: AHSG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AHSG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHSG were set to PMID: 28054173; 9395485; 31288248; 17389622
Phenotypes for gene: AHSG were set to ?Alopecia-intellectual disability syndrome 1 MIM#203650; infantile cortical hyperostosis
Review for gene: AHSG was set to RED
Added comment: PMID: 28054173 - 7 relatives within a large consanguinous fam w/ alopecia and ID, and a hom missense (p.Arg317His). Modelling predicts this variant to be a phosphorylation site, functional studies show a difference in protein size. Unclear biological significance.
Alt change with stronger GS (p.(Arg317Cys)) is a common poly with 19 homozygotes in gnomAD.

No hom PTCs in gnomAD

PMID: 9395485 - K/O mouse model shows no gross anatomical abnormalities, were fertile and "healthy". No mentioned of ID, alopecia
PMID: 17389622 - K/O mouse model on the calcification resistant genetic background C57BL/6, shows uraemia and phosphate challenge. No mentioned of ID, alopecia

PMID: 31288248 - 1 hom infant (p.K2*, within 5' NMD escape region) with infantile cortical hyperostosis, loss of enzyme in patient serum shown by ELISA. No mentioned of ID, alopecia
Sources: Literature
Mendeliome v0.12713 VPS16 Ain Roesley Phenotypes for gene: VPS16 were changed from Dystonia 30, MIM#619291 to Dystonia 30, MIM#619291; mucopolysaccharidosis-like disorder, VPS16-related MONDO#0100365
Mendeliome v0.12711 MDFIC Belinda Chong gene: MDFIC was added
gene: MDFIC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDFIC were set to 35235341
Phenotypes for gene: MDFIC were set to Central conducting lymphatic anomaly with lymphedema
Review for gene: MDFIC was set to GREEN
Added comment: Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise.

Seven individuals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax.
Sources: Literature
Mendeliome v0.12711 ATP2B1 Daniel Flanagan gene: ATP2B1 was added
gene: ATP2B1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATP2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B1 were set to PMID: 35358416
Phenotypes for gene: ATP2B1 were set to Neurodevelopmental delay; autism; seizures; distal limb abnormalities
Review for gene: ATP2B1 was set to GREEN
Added comment: 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism (5), dissimilar forms of seizures (6), and distal limb abnormalities (4). 9 variants proven to be de novo, other 3 variants had unknown inheritance. 9 missense and 3 nonsense reported. Supporting functional analysis for missense.
Sources: Expert list
Mendeliome v0.12711 TNFSF4 Zornitza Stark Gene: tnfsf4 has been classified as Red List (Low Evidence).
Mendeliome v0.12709 VPS16 Ain Roesley reviewed gene: VPS16: Rating: GREEN; Mode of pathogenicity: None; Publications: 33938619, 34013567; Phenotypes: mucopolysaccharidosis-like disorder, VPS16-related MONDO#0100365; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12709 TNFSF4 Zornitza Stark Classified gene: TNFSF4 as Red List (low evidence)
Mendeliome v0.12709 TNFSF4 Zornitza Stark Gene: tnfsf4 has been classified as Red List (Low Evidence).
Mendeliome v0.12708 TNFSF11 Zornitza Stark Gene: tnfsf11 has been classified as Green List (High Evidence).
Mendeliome v0.12708 TNFSF11 Zornitza Stark Phenotypes for gene: TNFSF11 were changed from to Osteopetrosis, autosomal recessive 2, MIM# 259710
Mendeliome v0.12705 TNFSF11 Zornitza Stark reviewed gene: TNFSF11: Rating: GREEN; Mode of pathogenicity: None; Publications: 17632511; Phenotypes: Osteopetrosis, autosomal recessive 2, MIM# 259710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12705 TNFRSF11B Zornitza Stark Gene: tnfrsf11b has been classified as Green List (High Evidence).
Mendeliome v0.12702 TMEM240 Zornitza Stark Gene: tmem240 has been classified as Green List (High Evidence).
Mendeliome v0.12699 TMEM127 Zornitza Stark Gene: tmem127 has been classified as Green List (High Evidence).
Mendeliome v0.12697 TMEM126B Zornitza Stark Gene: tmem126b has been classified as Green List (High Evidence).
Mendeliome v0.12694 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Green List (High Evidence).
Mendeliome v0.12691 TMEM106B Zornitza Stark changed review comment from: Cerebellar signs including ataxia prominent.; to: Hypomyelinating leukodystrophy-16 is an autosomal dominant neurologic disorder characterized by onset of hypotonia, nystagmus, and mildly delayed motor development in infancy. Affected individuals have motor disabilities, including ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties. Brain imaging typically shows hypomyelination, leukodystrophy, and thin corpus callosum.

At least 5 unrelated individuals reported.
Mendeliome v0.12691 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Mendeliome v0.12691 RAPSN Zornitza Stark Phenotypes for gene: RAPSN were changed from to Fetal akinesia deformation sequence 2 (MIM#618388); Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency (MIM#616326)
Mendeliome v0.12688 RAD51C Zornitza Stark Gene: rad51c has been classified as Green List (High Evidence).
Mendeliome v0.12684 SLC25A26 Zornitza Stark Gene: slc25a26 has been classified as Green List (High Evidence).
Mendeliome v0.12684 GGN Zornitza Stark Gene: ggn has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12684 GGN Zornitza Stark Classified gene: GGN as Amber List (moderate evidence)
Mendeliome v0.12684 GGN Zornitza Stark Gene: ggn has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12679 SLC25A3 Zornitza Stark Gene: slc25a3 has been classified as Green List (High Evidence).
Mendeliome v0.12676 RAPSN Crystle Lee reviewed gene: RAPSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 18252226, 19620612, 22482962, 28495245, 18179903, 28495245; Phenotypes: Fetal akinesia deformation sequence 2 (MIM#618388), Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency (MIM#616326); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12676 SLC25A4 Zornitza Stark Gene: slc25a4 has been classified as Green List (High Evidence).
Mendeliome v0.12676 SLC25A4 Zornitza Stark Phenotypes for gene: SLC25A4 were changed from to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283
Mendeliome v0.12673 SLC25A4 Zornitza Stark reviewed gene: SLC25A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30046662, 30013777, 29654543, 28823815; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184, Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12673 SLC25A42 Zornitza Stark Gene: slc25a42 has been classified as Green List (High Evidence).
Mendeliome v0.12673 SLC25A42 Zornitza Stark Phenotypes for gene: SLC25A42 were changed from to Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416
Mendeliome v0.12670 SLC25A42 Zornitza Stark reviewed gene: SLC25A42: Rating: GREEN; Mode of pathogenicity: None; Publications: 26541337, 29327420, 29923093, 34258143; Phenotypes: Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12670 SLC2A10 Zornitza Stark Gene: slc2a10 has been classified as Green List (High Evidence).
Mendeliome v0.12670 SLC2A10 Zornitza Stark Phenotypes for gene: SLC2A10 were changed from to Arterial tortuosity syndrome, MIM# 208050
Mendeliome v0.12667 SLC2A10 Zornitza Stark reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 16550171, 17935213; Phenotypes: Arterial tortuosity syndrome, MIM# 208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12667 SLC2A2 Zornitza Stark changed review comment from: Fanconi-Bickel syndrome is a rare but well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose.

> 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2.; to: Fanconi-Bickel syndrome is characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose.

> 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2.
Mendeliome v0.12667 SLC2A2 Zornitza Stark Gene: slc2a2 has been classified as Green List (High Evidence).
Mendeliome v0.12664 SLC2A3 Zornitza Stark Gene: slc2a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12664 SLC2A3 Zornitza Stark Classified gene: SLC2A3 as Red List (low evidence)
Mendeliome v0.12664 SLC2A3 Zornitza Stark Gene: slc2a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12663 SLC2A4 Zornitza Stark Gene: slc2a4 has been classified as Red List (Low Evidence).
Mendeliome v0.12663 SLC2A4 Zornitza Stark Classified gene: SLC2A4 as Red List (low evidence)
Mendeliome v0.12663 SLC2A4 Zornitza Stark Gene: slc2a4 has been classified as Red List (Low Evidence).
Mendeliome v0.12662 SORT1 Zornitza Stark Gene: sort1 has been classified as Red List (Low Evidence).
Mendeliome v0.12662 SORT1 Zornitza Stark Phenotypes for gene: SORT1 were changed from to Low density lipoprotein cholesterol level QTL6] 613589
Mendeliome v0.12660 SORT1 Zornitza Stark Classified gene: SORT1 as Red List (low evidence)
Mendeliome v0.12660 SORT1 Zornitza Stark Gene: sort1 has been classified as Red List (Low Evidence).
Mendeliome v0.12659 SORT1 Zornitza Stark reviewed gene: SORT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Low density lipoprotein cholesterol level QTL6] 613589; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12659 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Mendeliome v0.12656 SOX17 Zornitza Stark Gene: sox17 has been classified as Green List (High Evidence).
Mendeliome v0.12656 SOX17 Zornitza Stark Phenotypes for gene: SOX17 were changed from to Vesicoureteral reflux 3 MIM#613674; Pulmonary arterial hypertension, MONDO:0015924
Mendeliome v0.12653 SOX17 Zornitza Stark reviewed gene: SOX17: Rating: GREEN; Mode of pathogenicity: None; Publications: 29650961, 31406341, 20960469; Phenotypes: Vesicoureteral reflux 3 MIM#613674, Pulmonary arterial hypertension, MONDO:0015924; Mode of inheritance: None
Mendeliome v0.12653 SOX18 Zornitza Stark Gene: sox18 has been classified as Green List (High Evidence).
Mendeliome v0.12653 SOX18 Zornitza Stark Phenotypes for gene: SOX18 were changed from to Hypotrichosis-lymphedema-telangiectasia syndrome, MIM# 607823; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MIM# 137940
Mendeliome v0.12650 SOX18 Zornitza Stark reviewed gene: SOX18: Rating: GREEN; Mode of pathogenicity: None; Publications: 12740761, 24697860, 2484451, 26148450, 33851505; Phenotypes: Hypotrichosis-lymphedema-telangiectasia syndrome, MIM# 607823, Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MIM# 137940; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12650 SOX5 Zornitza Stark Gene: sox5 has been classified as Green List (High Evidence).
Mendeliome v0.12647 SOX9 Zornitza Stark Gene: sox9 has been classified as Green List (High Evidence).
Mendeliome v0.12647 SOX9 Zornitza Stark Phenotypes for gene: SOX9 were changed from to Campomelic dysplasia, MIM# 114290; Campomelic dysplasia, MONDO:0007251
Mendeliome v0.12644 SOX9 Zornitza Stark reviewed gene: SOX9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Campomelic dysplasia, MIM# 114290, Campomelic dysplasia, MONDO:0007251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12644 NKX2-1 Zornitza Stark reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978, Chorea, hereditary benign MIM#118700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12644 SP7 Zornitza Stark Gene: sp7 has been classified as Green List (High Evidence).
Mendeliome v0.12644 SP7 Zornitza Stark Phenotypes for gene: SP7 were changed from to Osteogenesis imperfecta type 12, MONDO:0013460; Osteogenesis imperfecta, type XII, OMIM:613849
Mendeliome v0.12641 SP7 Zornitza Stark reviewed gene: SP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 20579626, 29382611, 35367406, 34091789, 32413570; Phenotypes: Osteogenesis imperfecta type 12, MONDO:0013460, Osteogenesis imperfecta, type XII, OMIM:613849; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12641 SPAG7 Zornitza Stark Gene: spag7 has been classified as Red List (Low Evidence).
Mendeliome v0.12638 SPAG7 Zornitza Stark Classified gene: SPAG7 as Red List (low evidence)
Mendeliome v0.12638 SPAG7 Zornitza Stark Gene: spag7 has been classified as Red List (Low Evidence).
Mendeliome v0.12637 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Mendeliome v0.12634 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Mendeliome v0.12631 SPECC1L Zornitza Stark edited their review of gene: SPECC1L: Added comment: Well established gene-disease associations with Teebi and Opitz GBBB.

Single individual reported with oblique facial cleft, some supportive functional data.; Changed publications: 25412741, 26111080, 21703590; Changed phenotypes: Hypertelorism, Teebi type, MIM# 145420, Opitz GBBB syndrome, type II, MIM#145410
Mendeliome v0.12631 SPECC1L Zornitza Stark edited their review of gene: SPECC1L: Changed phenotypes: Hypertelorism, Teebi type, MIM# 145420, Opitz GBBB syndrome, type II, MIM#145410, Craniosynostosis
Mendeliome v0.12631 SSR4 Zornitza Stark Gene: ssr4 has been classified as Green List (High Evidence).
Mendeliome v0.12628 SRY Zornitza Stark Gene: sry has been classified as Green List (High Evidence).
Mendeliome v0.12625 SRP54 Zornitza Stark Gene: srp54 has been classified as Green List (High Evidence).
Mendeliome v0.12622 SRD5A2 Zornitza Stark Gene: srd5a2 has been classified as Green List (High Evidence).
Mendeliome v0.12619 SPRY1 Zornitza Stark Gene: spry1 has been classified as Red List (Low Evidence).
Mendeliome v0.12619 SPRY1 Zornitza Stark Classified gene: SPRY1 as Red List (low evidence)
Mendeliome v0.12619 SPRY1 Zornitza Stark Gene: spry1 has been classified as Red List (Low Evidence).
Mendeliome v0.12618 SPINK5 Zornitza Stark Gene: spink5 has been classified as Green List (High Evidence).
Mendeliome v0.12615 SPINK1 Zornitza Stark Gene: spink1 has been classified as Green List (High Evidence).
Mendeliome v0.12612 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, MIM# 607259 to Spastic paraplegia 7, autosomal recessive, MIM# 607259; Autosomal dominant optic atrophy, MONDO:0020250
Mendeliome v0.12610 SPG7 Zornitza Stark changed review comment from: SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes.

Well established for bi-allelic variants.

Enrichment of mono-allelic variants reported in a couple of cohorts, although a recent one suggests digenic inheritance.; to: SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes.

Well established for bi-allelic variants.

Enrichment of mono-allelic variants reported in a couple of cohorts, although a recent one suggests digenic inheritance.

Association with OA: 7 families reported for AD OA, including 5 missense and 2 frameshift variants, PMID 32548275
Mendeliome v0.12610 SPG7 Zornitza Stark edited their review of gene: SPG7: Changed publications: 9635427, 9635427, 16534102, 18799786, 22571692, 34500365, 33598982, 32548275; Changed phenotypes: Spastic paraplegia 7, autosomal recessive, MIM# 607259, Autosomal dominant optic atrophy, MONDO:0020250; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12610 SPG7 Zornitza Stark Gene: spg7 has been classified as Green List (High Evidence).
Mendeliome v0.12610 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from to Spastic paraplegia 7, autosomal recessive, MIM# 607259
Mendeliome v0.12607 SPG7 Zornitza Stark reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 9635427, 9635427, 16534102, 18799786, 22571692, 34500365, 33598982; Phenotypes: Spastic paraplegia 7, autosomal recessive, MIM# 607259; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12607 RSPO4 Zornitza Stark Gene: rspo4 has been classified as Green List (High Evidence).
Mendeliome v0.12604 RTN4IP1 Zornitza Stark Gene: rtn4ip1 has been classified as Green List (High Evidence).
Mendeliome v0.12601 RUNX1 Zornitza Stark Gene: runx1 has been classified as Green List (High Evidence).
Mendeliome v0.12598 PAX6 Zornitza Stark Gene: pax6 has been classified as Green List (High Evidence).
Mendeliome v0.12598 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from to 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
Mendeliome v0.12595 PAX2 Zornitza Stark Gene: pax2 has been classified as Green List (High Evidence).
Mendeliome v0.12595 PAX2 Zornitza Stark Phenotypes for gene: PAX2 were changed from to Papillorenal syndrome, MIM# 120330; Renal coloboma syndrome, MONDO:0007352; Glomerulosclerosis, focal segmental, 7 - MIM#616002
Mendeliome v0.12592 TSEN15 Zornitza Stark Gene: tsen15 has been classified as Green List (High Evidence).
Mendeliome v0.12592 TSEN15 Zornitza Stark Phenotypes for gene: TSEN15 were changed from to Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874
Mendeliome v0.12589 TSEN15 Zornitza Stark reviewed gene: TSEN15: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12589 RAB33B Zornitza Stark Gene: rab33b has been classified as Green List (High Evidence).
Mendeliome v0.12589 RAB33B Zornitza Stark Phenotypes for gene: RAB33B were changed from to Smith-McCort dysplasia 2 (MIM#615222)
Mendeliome v0.12586 RAB28 Zornitza Stark Gene: rab28 has been classified as Green List (High Evidence).
Mendeliome v0.12583 PAM16 Zornitza Stark Gene: pam16 has been classified as Green List (High Evidence).
Mendeliome v0.12583 PAM16 Zornitza Stark Phenotypes for gene: PAM16 were changed from to Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, OMIM # 613320
Mendeliome v0.12580 PALLD Zornitza Stark Gene: palld has been classified as Red List (Low Evidence).
Mendeliome v0.12580 PALLD Zornitza Stark Classified gene: PALLD as Red List (low evidence)
Mendeliome v0.12580 PALLD Zornitza Stark Gene: palld has been classified as Red List (Low Evidence).
Mendeliome v0.12578 AMPD3 Zornitza Stark Gene: ampd3 has been classified as Red List (Low Evidence).
Mendeliome v0.12575 AMPD3 Zornitza Stark Classified gene: AMPD3 as Red List (low evidence)
Mendeliome v0.12575 AMPD3 Zornitza Stark Gene: ampd3 has been classified as Red List (Low Evidence).
Mendeliome v0.12573 PAX6 Krithika Murali reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31700164, 30986449, 29930474, 22171686; Phenotypes: ?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; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12573 PAX2 Krithika Murali reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21654726, 24676634, 31060108, 32203253; Phenotypes: Papillorenal syndrome, MIM# 120330, Renal coloboma syndrome, MONDO:0007352, Glomerulosclerosis, focal segmental, 7 - MIM#616002; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12573 TSEN15 Manny Jacobs reviewed gene: TSEN15: Rating: ; Mode of pathogenicity: None; Publications: PMID: 25558065, 27392077; Phenotypes: Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874; Mode of inheritance: None
Mendeliome v0.12573 RAB33B Crystle Lee reviewed gene: RAB33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 22652534, 28127940, 23042644, 34284742; Phenotypes: Smith-McCort dysplasia 2 (MIM#615222); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12571 SERPINC1 Zornitza Stark Gene: serpinc1 has been classified as Green List (High Evidence).
Mendeliome v0.12568 SERPINB8 Zornitza Stark Gene: serpinb8 has been classified as Green List (High Evidence).
Mendeliome v0.12565 SERPINB6 Zornitza Stark Gene: serpinb6 has been classified as Green List (High Evidence).
Mendeliome v0.12565 SERPINB6 Zornitza Stark Phenotypes for gene: SERPINB6 were changed from to Deafness, autosomal recessive 91, MIM# 613453
Mendeliome v0.12561 PAM16 Krithika Murali reviewed gene: PAM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 24786642, 27354339; Phenotypes: Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, OMIM # 613320; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12561 CCM2 Ain Roesley Gene: ccm2 has been classified as Green List (High Evidence).
Mendeliome v0.12559 CCL2 Ain Roesley Gene: ccl2 has been classified as Red List (Low Evidence).
Mendeliome v0.12559 CCL2 Ain Roesley Phenotypes for gene: CCL2 were changed from to {HIV-1, resistance to} MIM#609423; {Mycobacterium tuberculosis, susceptibility to} MIM#607948; {Spina bifida, susceptibility to} MIM#182940
Mendeliome v0.12559 CCL2 Ain Roesley Classified gene: CCL2 as Red List (low evidence)
Mendeliome v0.12559 CCL2 Ain Roesley Gene: ccl2 has been classified as Red List (Low Evidence).
Mendeliome v0.12558 CCL2 Ain Roesley reviewed gene: CCL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {HIV-1, resistance to} MIM#609423, {Mycobacterium tuberculosis, susceptibility to} MIM#607948, {Spina bifida, susceptibility to} MIM#182940; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.12558 ANK1 Elena Savva Phenotypes for gene: ANK1 were changed from Spherocytosis, type 1 MIM#182900 to Spherocytosis, type 1 MIM#182900
Mendeliome v0.12557 CCDC88A Ain Roesley Gene: ccdc88a has been classified as Green List (High Evidence).
Mendeliome v0.12556 ANK1 Elena Savva Phenotypes for gene: ANK1 were changed from to Spherocytosis, type 1 MIM#182900
Mendeliome v0.12555 ANK1 Elena Savva Gene: ank1 has been classified as Green List (High Evidence).
Mendeliome v0.12554 ANK1 Elena Savva reviewed gene: ANK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8640229; Phenotypes: Spherocytosis, type 1 MIM#182900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12554 ANKH Elena Savva Gene: ankh has been classified as Green List (High Evidence).
Mendeliome v0.12554 CCDC50 Ain Roesley Gene: ccdc50 has been classified as Green List (High Evidence).
Mendeliome v0.12553 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from Microcephaly 16, primary, autosomal recessive, MIM# 616681 to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12552 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from Microcephaly 16, primary, autosomal recessive, MIM# 616681 to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12550 ANKH Elena Savva Phenotypes for gene: ANKH were changed from to Chondrocalcinosis 2 MIM#118600; Craniometaphyseal dysplasia MIM#123000
Mendeliome v0.12548 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12547 ANKLE2 Elena Savva Gene: ankle2 has been classified as Green List (High Evidence).
Mendeliome v0.12546 ANKH Elena Savva reviewed gene: ANKH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32366894; Phenotypes: Chondrocalcinosis 2 MIM#118600, Craniometaphyseal dysplasia MIM#123000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.12546 CAV3 Ain Roesley Gene: cav3 has been classified as Green List (High Evidence).
Mendeliome v0.12542 CATSPER2 Ain Roesley Gene: catsper2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12542 CATSPER2 Ain Roesley Classified gene: CATSPER2 as Amber List (moderate evidence)
Mendeliome v0.12542 CATSPER2 Ain Roesley Gene: catsper2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12539 ANGPTL3 Elena Savva Gene: angptl3 has been classified as Green List (High Evidence).
Mendeliome v0.12536 CATSPER1 Ain Roesley Gene: catsper1 has been classified as Green List (High Evidence).
Mendeliome v0.12534 ETFA Bryony Thompson Gene: etfa has been classified as Green List (High Evidence).
Mendeliome v0.12533 ERLIN2 Bryony Thompson Gene: erlin2 has been classified as Green List (High Evidence).
Mendeliome v0.12532 TSHB Zornitza Stark Gene: tshb has been classified as Green List (High Evidence).
Mendeliome v0.12528 TSHR Zornitza Stark Gene: tshr has been classified as Green List (High Evidence).
Mendeliome v0.12525 CAT Ain Roesley Gene: cat has been classified as Green List (High Evidence).
Mendeliome v0.12523 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12520 TSPAN7 Zornitza Stark Classified gene: TSPAN7 as Amber List (moderate evidence)
Mendeliome v0.12520 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12518 AMT Elena Savva Gene: amt has been classified as Green List (High Evidence).
Mendeliome v0.12518 EPX Bryony Thompson Gene: epx has been classified as Red List (Low Evidence).
Mendeliome v0.12518 EPX Bryony Thompson Phenotypes for gene: EPX were changed from to [Eosinophil peroxidase deficiency] MIM#261500
Mendeliome v0.12516 AMHR2 Elena Savva Gene: amhr2 has been classified as Green List (High Evidence).
Mendeliome v0.12516 AMHR2 Elena Savva Phenotypes for gene: AMHR2 were changed from to Persistent Mullerian duct syndrome, type II MIM#261550
Mendeliome v0.12514 ALX4 Elena Savva Gene: alx4 has been classified as Green List (High Evidence).
Mendeliome v0.12514 AMHR2 Elena Savva reviewed gene: AMHR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34810374; Phenotypes: Persistent Mullerian duct syndrome, type II MIM#261550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12512 ALX4 Elena Savva Phenotypes for gene: ALX4 were changed from to Frontonasal dysplasia 2 MIM# 613451; Parietal foramina 2 MIM# 609597; {Craniosynostosis 5, susceptibility to} MIM#615529
Mendeliome v0.12511 EPX Bryony Thompson Classified gene: EPX as Red List (low evidence)
Mendeliome v0.12511 EPX Bryony Thompson Gene: epx has been classified as Red List (Low Evidence).
Mendeliome v0.12510 EPX Bryony Thompson reviewed gene: EPX: Rating: RED; Mode of pathogenicity: None; Publications: 7809065, 11241847; Phenotypes: [Eosinophil peroxidase deficiency] MIM#261500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12510 ALX4 Elena Savva reviewed gene: ALX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22829454, 34586326; Phenotypes: Frontonasal dysplasia 2 MIM# 613451, Parietal foramina 2 MIM# 609597, {Craniosynostosis 5, susceptibility to} MIM#615529; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12508 ALMS1 Elena Savva Gene: alms1 has been classified as Green List (High Evidence).
Mendeliome v0.12508 ALDH6A1 Elena Savva Gene: aldh6a1 has been classified as Green List (High Evidence).
Mendeliome v0.12508 ALDH18A1 Elena Savva Phenotypes for gene: ALDH18A1 were changed from Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism to Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism
Mendeliome v0.12505 ALDH18A1 Elena Savva Phenotypes for gene: ALDH18A1 were changed from to Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism
Mendeliome v0.12504 ALDH18A1 Elena Savva Gene: aldh18a1 has been classified as Green List (High Evidence).
Mendeliome v0.12503 CASR Ain Roesley Gene: casr has been classified as Green List (High Evidence).
Mendeliome v0.12500 CASQ1 Ain Roesley Gene: casq1 has been classified as Green List (High Evidence).
Mendeliome v0.12498 SERPINB6 Samantha Ayres reviewed gene: SERPINB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20451170, 25719458, 23669344; Phenotypes: Deafness, autosomal recessive 91, MIM# 613453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12498 TMEM98 Zornitza Stark Gene: tmem98 has been classified as Green List (High Evidence).
Mendeliome v0.12495 TMEM70 Zornitza Stark Gene: tmem70 has been classified as Green List (High Evidence).
Mendeliome v0.12492 TMEM38B Zornitza Stark Gene: tmem38b has been classified as Green List (High Evidence).
Mendeliome v0.12492 TMEM38B Zornitza Stark Phenotypes for gene: TMEM38B were changed from to Osteogenesis imperfecta, type XIV, MIM# 615066
Mendeliome v0.12489 TMEM38B Zornitza Stark reviewed gene: TMEM38B: Rating: GREEN; Mode of pathogenicity: None; Publications: 23054245; Phenotypes: Osteogenesis imperfecta, type XIV, MIM# 615066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12489 TMEM199 Zornitza Stark Gene: tmem199 has been classified as Green List (High Evidence).
Mendeliome v0.12486 TMEM173 Zornitza Stark Gene: tmem173 has been classified as Green List (High Evidence).
Mendeliome v0.12483 TMC6 Zornitza Stark Gene: tmc6 has been classified as Green List (High Evidence).
Mendeliome v0.12483 TMC6 Zornitza Stark Phenotypes for gene: TMC6 were changed from to Epidermodysplasia verruciformis, MIM# 226400
Mendeliome v0.12480 TMC6 Zornitza Stark reviewed gene: TMC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 12426567, 15042430]; Phenotypes: Epidermodysplasia verruciformis, MIM# 226400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12480 TLR5 Zornitza Stark Gene: tlr5 has been classified as Red List (Low Evidence).
Mendeliome v0.12480 TLR5 Zornitza Stark Classified gene: TLR5 as Red List (low evidence)
Mendeliome v0.12480 TLR5 Zornitza Stark Gene: tlr5 has been classified as Red List (Low Evidence).
Mendeliome v0.12479 TLR3 Zornitza Stark Gene: tlr3 has been classified as Green List (High Evidence).
Mendeliome v0.12476 TLR2 Zornitza Stark Gene: tlr2 has been classified as Red List (Low Evidence).
Mendeliome v0.12476 TLR2 Zornitza Stark Classified gene: TLR2 as Red List (low evidence)
Mendeliome v0.12476 TLR2 Zornitza Stark Gene: tlr2 has been classified as Red List (Low Evidence).
Mendeliome v0.12475 FTCD Zornitza Stark Gene: ftcd has been classified as Green List (High Evidence).
Mendeliome v0.12475 FTCD Zornitza Stark Phenotypes for gene: FTCD were changed from Glutamate formiminotransferase deficiency MIM#229100; Disorders of histidine, tryptophan or lysine metabolism to Glutamate formiminotransferase deficiency MIM#229100; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v0.12472 FTCD Zornitza Stark Gene: ftcd has been classified as Green List (High Evidence).
Mendeliome v0.12472 FTCD Zornitza Stark Phenotypes for gene: FTCD were changed from to Glutamate formiminotransferase deficiency MIM#229100; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v0.12469 FGF14 Zornitza Stark Gene: fgf14 has been classified as Green List (High Evidence).
Mendeliome v0.12467 FAT4 Zornitza Stark Gene: fat4 has been classified as Green List (High Evidence).
Mendeliome v0.12467 FAT4 Zornitza Stark Phenotypes for gene: FAT4 were changed from to Hennekam lymphangiectasia-lymphedema syndrome 2 MIM#616006; Van Maldergem syndrome 2 MIM#615546
Mendeliome v0.12464 ERLIN1 Zornitza Stark Gene: erlin1 has been classified as Green List (High Evidence).
Mendeliome v0.12464 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Mendeliome v0.12460 SLC30A2 Zornitza Stark Gene: slc30a2 has been classified as Green List (High Evidence).
Mendeliome v0.12460 SLC30A2 Zornitza Stark Phenotypes for gene: SLC30A2 were changed from to Zinc deficiency, transient neonatal , MIM#608118
Mendeliome v0.12457 SLC30A2 Zornitza Stark reviewed gene: SLC30A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17065149, 22733820, 32278324, 30450693, 28665435; Phenotypes: Zinc deficiency, transient neonatal , MIM#608118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12457 SLC2A9 Zornitza Stark Gene: slc2a9 has been classified as Green List (High Evidence).
Mendeliome v0.12454 RIPOR2 Zornitza Stark Phenotypes for gene: RIPOR2 were changed from Deafness, autosomal recessive 104, MIM# 616515; Deafness, autosomal dominant to Deafness, autosomal recessive 104, MIM# 616515; Deafness, autosomal dominant 21, MIM# 607017
Mendeliome v0.12453 RIPOR2 Zornitza Stark edited their review of gene: RIPOR2: Changed phenotypes: Deafness, autosomal recessive 104, MIM# 616515, Deafness, autosomal dominant 21, MIM# 607017
Mendeliome v0.12451 EPS8 Bryony Thompson reviewed gene: EPS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24741995, 27344577, 30303587, 34637946, 21526224; Phenotypes: Autosomal recessive nonsyndromic hearing loss 102 MONDO:0014428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12449 SLC30A8 Zornitza Stark Gene: slc30a8 has been classified as Red List (Low Evidence).
Mendeliome v0.12446 SLC30A8 Zornitza Stark Classified gene: SLC30A8 as Red List (low evidence)
Mendeliome v0.12446 SLC30A8 Zornitza Stark Gene: slc30a8 has been classified as Red List (Low Evidence).
Mendeliome v0.12445 SLC34A1 Zornitza Stark changed review comment from: Infantile hypercalcaemia and bi-allelic variants: More than 5 unrelated families reported.

Nephrolithiasis and mono-allelic variants: multiple families reported.; to: Infantile hypercalcaemia and bi-allelic variants: More than 5 unrelated families reported.

Nephrolithiasis and mono-allelic variants: multiple families reported.

Single family reported with renal Fanconi and homozygous variant.
Mendeliome v0.12445 SLC34A1 Zornitza Stark Gene: slc34a1 has been classified as Green List (High Evidence).
Mendeliome v0.12445 SLC34A1 Zornitza Stark Phenotypes for gene: SLC34A1 were changed from to Hypercalcaemia, infantile, 2 MIM#616963; Nephrolithiasis/osteoporosis, hypophosphatemic, 1 612286
Mendeliome v0.12442 SLC34A1 Zornitza Stark reviewed gene: SLC34A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26047794, 33516786, 33099630, 32866123, 31188746, 30943683, 12324554, 32216560, 30778725; Phenotypes: Hypercalcaemia, infantile, 2 MIM#616963, Nephrolithiasis/osteoporosis, hypophosphatemic, 1 612286; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12442 SLC34A2 Zornitza Stark Gene: slc34a2 has been classified as Green List (High Evidence).
Mendeliome v0.12442 SLC34A2 Zornitza Stark Phenotypes for gene: SLC34A2 were changed from to Pulmonary alveolar microlithiasis, MIM# 265100
Mendeliome v0.12439 SLC34A2 Zornitza Stark reviewed gene: SLC34A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16960801, 34581165, 33884208, 32328294, 31941744; Phenotypes: Pulmonary alveolar microlithiasis, MIM# 265100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12439 SLC35A1 Zornitza Stark Gene: slc35a1 has been classified as Green List (High Evidence).
Mendeliome v0.12439 EPO Bryony Thompson Gene: epo has been classified as Green List (High Evidence).
Mendeliome v0.12436 EPO Bryony Thompson Phenotypes for gene: EPO were changed from to erythrocytosis, familial, 5 MONDO:0033483
Mendeliome v0.12435 SLC39A13 Zornitza Stark Gene: slc39a13 has been classified as Green List (High Evidence).
Mendeliome v0.12432 SLC39A5 Zornitza Stark Gene: slc39a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12430 EPO Bryony Thompson changed review comment from: PMID: 27651169, 29514032, 25985138 - At least 4 families reported with heterozygous variants segregating with erythrocytosis. Mechanism of disease is gain-of-function. Frameshift variants identified (c.32delG, c.19delC) use of an alternative promoter (P2) in intron 1 causing the production of functional transcripts and increased amounts of biologically active EPO compared to controls, and 5’UTR conserved variant (c.‐136G>A) and expected to have a similar mechanism.

PMID: 28283061 - single proband from a consanguineous family with severe anaemia (Diamond-Blackfan anaemia phenotype) reported with a homozygous missense (R150Q) showing a mild reduction in its affinity for the EPO receptor; to: PMID: 27651169, 29514032, 25985138 - At least 4 families reported with heterozygous variants segregating with erythrocytosis. Mechanism of disease is gain-of-function. Frameshift variants identified (c.32delG, c.19delC) use of an alternative promoter (P2) in intron 1 causing the production of functional transcripts and increased amounts of biologically active EPO compared to controls, and 5’UTR conserved variant (c.‐136G>A) expected to have a similar mechanism.

PMID: 28283061 - single proband from a consanguineous family with severe anaemia (Diamond-Blackfan anaemia phenotype) reported with a homozygous missense (R150Q) showing a mild reduction in its affinity for the EPO receptor
Mendeliome v0.12429 SLC39A5 Zornitza Stark Classified gene: SLC39A5 as Amber List (moderate evidence)
Mendeliome v0.12429 SLC39A5 Zornitza Stark Gene: slc39a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12426 EPM2A Bryony Thompson Gene: epm2a has been classified as Green List (High Evidence).
Mendeliome v0.12425 EPO Bryony Thompson reviewed gene: EPO: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27651169, 29514032, 25985138, 28283061; Phenotypes: erythrocytosis, familial, 5 MONDO:0033483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12422 EPHA3 Bryony Thompson Gene: epha3 has been classified as Red List (Low Evidence).
Mendeliome v0.12422 EPHA3 Bryony Thompson Classified gene: EPHA3 as Red List (low evidence)
Mendeliome v0.12422 EPHA3 Bryony Thompson Gene: epha3 has been classified as Red List (Low Evidence).
Mendeliome v0.12421 EPHA2 Bryony Thompson Gene: epha2 has been classified as Green List (High Evidence).
Mendeliome v0.12420 SLC40A1 Zornitza Stark Gene: slc40a1 has been classified as Green List (High Evidence).
Mendeliome v0.12420 SLC40A1 Zornitza Stark Phenotypes for gene: SLC40A1 were changed from to Haemochromatosis, type 4, MIM# 606069
Mendeliome v0.12417 SLC40A1 Zornitza Stark reviewed gene: SLC40A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11431687, 11518736, 15956209, 16351644; Phenotypes: Haemochromatosis, type 4 606069; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12415 SLC4A11 Zornitza Stark Gene: slc4a11 has been classified as Green List (High Evidence).
Mendeliome v0.12415 SLC4A11 Zornitza Stark Phenotypes for gene: SLC4A11 were changed from to Corneal dystrophy, Fuchs endothelial, 4, MIM# 613268; Corneal endothelial dystrophy and perceptive deafness, MIM# 217400; Corneal endothelial dystrophy, autosomal recessive, MIM# 217700
Mendeliome v0.12413 SLC4A11 Zornitza Stark reviewed gene: SLC4A11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Corneal dystrophy, Fuchs endothelial, 4, MIM# 613268, Corneal endothelial dystrophy and perceptive deafness, MIM# 217400, Corneal endothelial dystrophy, autosomal recessive, MIM# 217700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12413 SLC4A4 Zornitza Stark Gene: slc4a4 has been classified as Green List (High Evidence).
Mendeliome v0.12413 SLC4A4 Zornitza Stark Phenotypes for gene: SLC4A4 were changed from to Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278; Hemiplegic migraine
Mendeliome v0.12410 SLC4A4 Zornitza Stark reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10545938, 11274232, 35260236, 33439394, 29914390; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278, Hemiplegic migraine; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12410 ENO3 Bryony Thompson Gene: eno3 has been classified as Green List (High Evidence).
Mendeliome v0.12407 ENG Bryony Thompson Gene: eng has been classified as Green List (High Evidence).
Mendeliome v0.12407 ENG Bryony Thompson Phenotypes for gene: ENG were changed from to hereditary hemorrhagic telangiectasia MONDO:0019180
Mendeliome v0.12404 ENG Bryony Thompson reviewed gene: ENG: Rating: GREEN; Mode of pathogenicity: None; Publications: 34012068, 30336550, 7894484, 10751092, 20414677, 30763665, 17384219, 20364125; Phenotypes: hereditary hemorrhagic telangiectasia MONDO:0019180; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12404 EMP2 Bryony Thompson Gene: emp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12401 EMP2 Bryony Thompson Classified gene: EMP2 as Amber List (moderate evidence)
Mendeliome v0.12401 EMP2 Bryony Thompson Gene: emp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12400 ELP2 Bryony Thompson Gene: elp2 has been classified as Green List (High Evidence).
Mendeliome v0.12400 ELP2 Bryony Thompson Phenotypes for gene: ELP2 were changed from to intellectual disability, autosomal recessive 58 MONDO:0014996
Mendeliome v0.12397 ELP2 Bryony Thompson reviewed gene: ELP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 25847581, 32573669, 34653680; Phenotypes: intellectual disability, autosomal recessive 58 MONDO:0014996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12397 ELOVL4 Bryony Thompson Gene: elovl4 has been classified as Green List (High Evidence).
Mendeliome v0.12397 ELOVL5 Bryony Thompson Gene: elovl5 has been classified as Green List (High Evidence).
Mendeliome v0.12396 ELOVL4 Bryony Thompson Phenotypes for gene: ELOVL4 were changed from to congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760; spinocerebellar ataxia type 34 MONDO:0007574; Stargardt disease MONDO:0019353
Mendeliome v0.12390 ELOVL4 Bryony Thompson reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11138005, 15028284, 11726641, 17208947, 22100072, 24566826, 34227061, 24571530, 26010696; Phenotypes: congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760, spinocerebellar ataxia type 34 MONDO:0007574, Stargardt disease MONDO:0019353; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12390 ELN Bryony Thompson Gene: eln has been classified as Green List (High Evidence).
Mendeliome v0.12390 ELN Bryony Thompson Phenotypes for gene: ELN were changed from to cutis laxa, autosomal dominant 1 MONDO:0007411; supravalvular aortic stenosis MONDO:0008504
Mendeliome v0.12387 ELN Bryony Thompson reviewed gene: ELN: Rating: GREEN; Mode of pathogenicity: None; Publications: 8132745, 9580666, 9873040, 10190324, 10190538, 22573328, 28383366; Phenotypes: cutis laxa, autosomal dominant 1 MONDO:0007411, supravalvular aortic stenosis MONDO:0008504; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12386 SLC52A2 Zornitza Stark Gene: slc52a2 has been classified as Green List (High Evidence).
Mendeliome v0.12384 SLC52A3 Zornitza Stark Gene: slc52a3 has been classified as Green List (High Evidence).
Mendeliome v0.12382 DVL2 Bryony Thompson Gene: dvl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12382 DVL2 Bryony Thompson Classified gene: DVL2 as Amber List (moderate evidence)
Mendeliome v0.12382 DVL2 Bryony Thompson Gene: dvl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12381 SLC5A2 Zornitza Stark Gene: slc5a2 has been classified as Green List (High Evidence).
Mendeliome v0.12381 DVL2 Bryony Thompson gene: DVL2 was added
gene: DVL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DVL2 were set to 35047859; 33599851; 30521570
Phenotypes for gene: DVL2 were set to Robinow syndrome MONDO:0019978
Review for gene: DVL2 was set to AMBER
Added comment: A single case with Robinow syndrome identified with a de novo frameshift variant in the last exon of the gene (c.2105dupC, p.Pro703Serfs*103). Also, a canine DVL2 frameshift variant has been associated with a Robinow-like syndrome in dogs, contributing to the brachycephalic phenotype and caudal vertebral anomalies.
Sources: Literature
Mendeliome v0.12379 SLC6A17 Zornitza Stark Gene: slc6a17 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12379 TAMM41 Bryony Thompson Gene: tamm41 has been classified as Green List (High Evidence).
Mendeliome v0.12379 TAMM41 Bryony Thompson Classified gene: TAMM41 as Green List (high evidence)
Mendeliome v0.12379 TAMM41 Bryony Thompson Gene: tamm41 has been classified as Green List (High Evidence).
Mendeliome v0.12378 TAMM41 Bryony Thompson gene: TAMM41 was added
gene: TAMM41 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TAMM41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAMM41 were set to 35321494; 29253589
Phenotypes for gene: TAMM41 were set to inborn mitochondrial metabolism disorder MONDO:0004069; hypotonia; developmental delay; myopathy; ptosis
Review for gene: TAMM41 was set to GREEN
Added comment: Three unrelated individuals with mitochondrial disease that share clinical features, including lethargy at birth, hypotonia, developmental delay, myopathy, and ptosis with biallelic variants. Tissue-specific observations on OXPHOS were identified, cardiolipin levels were unchanged in subject fibroblasts but significantly decreased in the skeletal muscle of affected individuals. The missense variants identified were defective in yeast models. In an in vitro cell model knockdown of TAMM41 resulted in decreased mitochondrial CDP diacylglycerol synthase activity, decreased cardiolipin levels and a decrease in oxygen consumption.
Sources: Literature
Mendeliome v0.12377 SLC6A17 Zornitza Stark Phenotypes for gene: SLC6A17 were changed from to Mental retardation, autosomal recessive 48, MIM# 616269
Mendeliome v0.12374 SLC6A17 Zornitza Stark Classified gene: SLC6A17 as Amber List (moderate evidence)
Mendeliome v0.12374 SLC6A17 Zornitza Stark Gene: slc6a17 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12373 SLC6A17 Zornitza Stark reviewed gene: SLC6A17: Rating: AMBER; Mode of pathogenicity: None; Publications: 25704603, 23672601; Phenotypes: Mental retardation, autosomal recessive 48, MIM# 616269; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12373 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Mendeliome v0.12371 BNIP1 Bryony Thompson Gene: bnip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12371 BNIP1 Bryony Thompson Classified gene: BNIP1 as Amber List (moderate evidence)
Mendeliome v0.12371 BNIP1 Bryony Thompson Gene: bnip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12370 BNIP1 Bryony Thompson gene: BNIP1 was added
gene: BNIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BNIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BNIP1 were set to 35266227; 31344970
Phenotypes for gene: BNIP1 were set to spondyloepiphyseal dysplasia MONDO:0016761
Review for gene: BNIP1 was set to AMBER
Added comment: Two apparently unrelated cases with spondyloepiphyseal dysplasia from India were identified with the same variant (c.84+3A>T). The kindred coefficient comparison of the 2 cases exome data suggested they were unrelated, however there was a stretch of shared homozygosity suggesting remote consanguinity. ~80% aberrantly spliced BNIP1 pre-mRNAs, reduced BNIP1 mRNA level to ~80%, and BNIP1 protein level reduction by ~50% were detected in one of the cases fibroblasts. A block at the terminal stage of autolysosome formation and/or clearance in patient fibroblasts was suggested based on the data. A drosophila model of the BNIP1 orthologue Sec20 also demonstrated defective autolysosome formation.
Sources: Literature
Mendeliome v0.12369 EIF4E Bryony Thompson Gene: eif4e has been classified as Red List (Low Evidence).
Mendeliome v0.12367 EIF4E Bryony Thompson Classified gene: EIF4E as Red List (low evidence)
Mendeliome v0.12367 EIF4E Bryony Thompson Gene: eif4e has been classified as Red List (Low Evidence).
Mendeliome v0.12366 TLL1 Zornitza Stark Gene: tll1 has been classified as Green List (High Evidence).
Mendeliome v0.12365 TK2 Zornitza Stark Gene: tk2 has been classified as Green List (High Evidence).
Mendeliome v0.12365 TK2 Zornitza Stark Phenotypes for gene: TK2 were changed from to Mitochondrial DNA depletion syndrome 2 (myopathic type), MIM# 609560; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3; MIM# 617069
Mendeliome v0.12362 TK2 Zornitza Stark reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11687801, 12391347, 12873860, 35286480, 35280287, 35094997; Phenotypes: Mitochondrial DNA depletion syndrome 2 (myopathic type), MIM# 609560, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3, MIM# 617069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12362 TJP2 Zornitza Stark Gene: tjp2 has been classified as Green List (High Evidence).
Mendeliome v0.12362 TJP2 Zornitza Stark Phenotypes for gene: TJP2 were changed from to Cholestasis, progressive familial intrahepatic 4, MIM# 615878; Hypercholanemia, familial 1, MIM# 607748
Mendeliome v0.12359 TJP2 Zornitza Stark reviewed gene: TJP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24614073, 25921221, 31696999, 12704386; Phenotypes: Cholestasis, progressive familial intrahepatic 4, MIM# 615878, Hypercholanemia, familial 1, MIM# 607748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12359 TIMP3 Zornitza Stark Gene: timp3 has been classified as Green List (High Evidence).
Mendeliome v0.12356 TIMM50 Zornitza Stark Gene: timm50 has been classified as Green List (High Evidence).
Mendeliome v0.12353 TIMM44 Zornitza Stark Gene: timm44 has been classified as Red List (Low Evidence).
Mendeliome v0.12353 TIMM44 Zornitza Stark Classified gene: TIMM44 as Red List (low evidence)
Mendeliome v0.12353 TIMM44 Zornitza Stark Gene: timm44 has been classified as Red List (Low Evidence).
Mendeliome v0.12352 TICAM1 Zornitza Stark Gene: ticam1 has been classified as Green List (High Evidence).
Mendeliome v0.12349 TTBK2 Zornitza Stark Gene: ttbk2 has been classified as Green List (High Evidence).
Mendeliome v0.12346 TTLL5 Zornitza Stark Gene: ttll5 has been classified as Green List (High Evidence).
Mendeliome v0.12343 TTR Zornitza Stark Gene: ttr has been classified as Green List (High Evidence).
Mendeliome v0.12343 TTR Zornitza Stark Phenotypes for gene: TTR were changed from to Amyloidosis, hereditary, transthyretin-related, MIM #105210; Carpal tunnel syndrome, familial, MIM# 115430
Mendeliome v0.12338 PADI6 Zornitza Stark Gene: padi6 has been classified as Green List (High Evidence).
Mendeliome v0.12335 PADI3 Zornitza Stark Gene: padi3 has been classified as Green List (High Evidence).
Mendeliome v0.12332 PACS2 Zornitza Stark Gene: pacs2 has been classified as Green List (High Evidence).
Mendeliome v0.12329 PABPN1 Zornitza Stark Gene: pabpn1 has been classified as Green List (High Evidence).
Mendeliome v0.12326 AGK Zornitza Stark Gene: agk has been classified as Green List (High Evidence).
Mendeliome v0.12323 EIF2B5 Bryony Thompson Gene: eif2b5 has been classified as Green List (High Evidence).
Mendeliome v0.12323 TTR Manny Jacobs reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:1570831, 1626570, 16115295, 16194874, 26537620; Phenotypes: Amyloidosis, hereditary, transthyretin-related, MIM #105210, Carpal tunnel syndrome, familial, MIM# 115430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12321 P3H2 Zornitza Stark Gene: p3h2 has been classified as Green List (High Evidence).
Mendeliome v0.12316 AKT3 Elena Savva Gene: akt3 has been classified as Green List (High Evidence).
Mendeliome v0.12316 EIF2B4 Bryony Thompson Gene: eif2b4 has been classified as Green List (High Evidence).
Mendeliome v0.12311 EIF2B3 Bryony Thompson Gene: eif2b3 has been classified as Green List (High Evidence).
Mendeliome v0.12311 AFP Zornitza Stark Added comment: Comment when marking as ready: Raised or low levels of AFP are observed in some medical conditions, kept Amber due to possible phenotypic overlap.
Mendeliome v0.12311 AFP Zornitza Stark Gene: afp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12311 AFP Zornitza Stark Phenotypes for gene: AFP were changed from to Alpha-fetoprotein deficiency MIM#615969; [Hereditary persistence of alpha-fetoprotein] MIM#615970
Mendeliome v0.12308 AFP Zornitza Stark Classified gene: AFP as Amber List (moderate evidence)
Mendeliome v0.12308 AFP Zornitza Stark Gene: afp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12304 AHCY Elena Savva Gene: ahcy has been classified as Green List (High Evidence).
Mendeliome v0.12302 EIF2B1 Bryony Thompson Gene: eif2b1 has been classified as Green List (High Evidence).
Mendeliome v0.12302 AGL Elena Savva Gene: agl has been classified as Green List (High Evidence).
Mendeliome v0.12298 EIF2AK3 Bryony Thompson Gene: eif2ak3 has been classified as Green List (High Evidence).
Mendeliome v0.12297 TIA1 Zornitza Stark Classified gene: TIA1 as Amber List (moderate evidence)
Mendeliome v0.12297 TIA1 Zornitza Stark Gene: tia1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12296 EIF2AK3 Bryony Thompson Phenotypes for gene: EIF2AK3 were changed from to Wolcott-Rallison syndrome MONDO:0009192; neonatal diabetes mellitus; epiphyseal dysplasia/osteopenia; hepatic/renal dysfunction; intellectual disability/developmental delay
Mendeliome v0.12295 TIA1 Zornitza Stark reviewed gene: TIA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29235362, 29886022, 29773329, 29699721, 29216908, 24659297, 29457785, 28817800, 23401021, 23401021; Phenotypes: Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133, Welander distal myopathy (MIM#604454); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12293 THSD1 Zornitza Stark Gene: thsd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12290 THSD1 Zornitza Stark Classified gene: THSD1 as Amber List (moderate evidence)
Mendeliome v0.12290 THSD1 Zornitza Stark Gene: thsd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12289 EFNA4 Bryony Thompson Gene: efna4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12289 EIF2AK3 Bryony Thompson reviewed gene: EIF2AK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10932183, 12960215, 16813601, 11997520, 20202148; Phenotypes: Wolcott-Rallison syndrome MONDO:0009192, neonatal diabetes mellitus, epiphyseal dysplasia/osteopenia, hepatic/renal dysfunction, intellectual disability/developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12289 EFNA4 Bryony Thompson Phenotypes for gene: EFNA4 were changed from to craniosynostosis MONDO:0015469
Mendeliome v0.12288 RBMX Zornitza Stark Gene: rbmx has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12288 RBMX Zornitza Stark Classified gene: RBMX as Amber List (moderate evidence)
Mendeliome v0.12288 RBMX Zornitza Stark Gene: rbmx has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12287 RBMX Zornitza Stark gene: RBMX was added
gene: RBMX was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: RBMX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RBMX were set to 25256757; 34260915
Phenotypes for gene: RBMX were set to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238
Review for gene: RBMX was set to AMBER
Added comment: Hemizygous truncating variant reported segregating in multiple affected individuals in a single family. Some supportive functional data.
Sources: Expert Review
Mendeliome v0.12284 EHBP1 Bryony Thompson Gene: ehbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.12283 EHBP1 Bryony Thompson Classified gene: EHBP1 as Red List (low evidence)
Mendeliome v0.12283 EHBP1 Bryony Thompson Gene: ehbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.12282 EDNRB Bryony Thompson Gene: ednrb has been classified as Green List (High Evidence).
Mendeliome v0.12282 EFNA4 Bryony Thompson Classified gene: EFNA4 as Amber List (moderate evidence)
Mendeliome v0.12282 EFNA4 Bryony Thompson Gene: efna4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12281 EFNA4 Bryony Thompson reviewed gene: EFNA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 16540516, 19201948, 19772933, 23983218, 29168297, 29215649, 33065355, 34586326; Phenotypes: craniosynostosis MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12281 AFP Elena Savva reviewed gene: AFP: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 15280901, 18854864; Phenotypes: Alpha-fetoprotein deficiency MIM#615969, [Hereditary persistence of alpha-fetoprotein] MIM#615970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12281 ADRB2 Elena Savva Gene: adrb2 has been classified as Red List (Low Evidence).
Mendeliome v0.12281 ADRB2 Elena Savva Phenotypes for gene: ADRB2 were changed from to Beta-2-adrenoreceptor agonist, reduced response to; {Asthma, nocturnal, susceptibility to} MIM#600807; {Obesity, susceptibility to} MIM#601665
Mendeliome v0.12280 ADRB2 Elena Savva Classified gene: ADRB2 as Red List (low evidence)
Mendeliome v0.12280 ADRB2 Elena Savva Gene: adrb2 has been classified as Red List (Low Evidence).
Mendeliome v0.12279 THRB Zornitza Stark Gene: thrb has been classified as Green List (High Evidence).
Mendeliome v0.12279 THRB Zornitza Stark Phenotypes for gene: THRB were changed from to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650
Mendeliome v0.12276 THRB Zornitza Stark reviewed gene: THRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25135573, 31590893; Phenotypes: Thyroid hormone resistance, MIM# 188570, Thyroid hormone resistance, autosomal recessive, MIM# 274300, Thyroid hormone resistance, selective pituitary, MIM# 145650; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12276 ADRB2 Elena Savva reviewed gene: ADRB2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 15724149; Phenotypes: Beta-2-adrenoreceptor agonist, reduced response to, {Asthma, nocturnal, susceptibility to} MIM#600807, {Obesity, susceptibility to} MIM#601665; Mode of inheritance: Unknown
Mendeliome v0.12276 SLC6A2 Zornitza Stark Gene: slc6a2 has been classified as Red List (Low Evidence).
Mendeliome v0.12273 SLC6A2 Zornitza Stark Classified gene: SLC6A2 as Red List (low evidence)
Mendeliome v0.12273 SLC6A2 Zornitza Stark Gene: slc6a2 has been classified as Red List (Low Evidence).
Mendeliome v0.12272 SMARCAD1 Zornitza Stark Gene: smarcad1 has been classified as Green List (High Evidence).
Mendeliome v0.12268 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Mendeliome v0.12268 SMARCB1 Zornitza Stark Phenotypes for gene: SMARCB1 were changed from to Coffin-Siris syndrome 3, MIM# 614608
Mendeliome v0.12265 SMARCB1 Zornitza Stark reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34205270, 31530938, 25168959; Phenotypes: Coffin-Siris syndrome 3, MIM# 614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12265 SMN2 Zornitza Stark Gene: smn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12263 SMN2 Zornitza Stark Classified gene: SMN2 as Amber List (moderate evidence)
Mendeliome v0.12263 SMN2 Zornitza Stark Gene: smn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12262 OTOG Zornitza Stark Gene: otog has been classified as Green List (High Evidence).
Mendeliome v0.12262 OTOG Zornitza Stark Phenotypes for gene: OTOG were changed from to Deafness, autosomal recessive 18B - MIM#614945
Mendeliome v0.12255 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Mendeliome v0.12253 OSTM1 Zornitza Stark Gene: ostm1 has been classified as Green List (High Evidence).
Mendeliome v0.12253 OSTM1 Zornitza Stark Phenotypes for gene: OSTM1 were changed from to Osteopetrosis, autosomal recessive 5 (MIM#259720)
Mendeliome v0.12250 OSMR Zornitza Stark Gene: osmr has been classified as Green List (High Evidence).
Mendeliome v0.12250 OSMR Zornitza Stark Phenotypes for gene: OSMR were changed from to Amyloidosis, primary localized cutaneous, 1 - MIM#105250
Mendeliome v0.12247 OSBPL2 Zornitza Stark Gene: osbpl2 has been classified as Green List (High Evidence).
Mendeliome v0.12244 OR2J3 Zornitza Stark Gene: or2j3 has been classified as Red List (Low Evidence).
Mendeliome v0.12244 OR2J3 Zornitza Stark Classified gene: OR2J3 as Red List (low evidence)
Mendeliome v0.12244 OR2J3 Zornitza Stark Gene: or2j3 has been classified as Red List (Low Evidence).
Mendeliome v0.12243 OPN1SW Zornitza Stark Gene: opn1sw has been classified as Green List (High Evidence).
Mendeliome v0.12240 OPN1MW Zornitza Stark Gene: opn1mw has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12237 OPN1MW Zornitza Stark Classified gene: OPN1MW as Amber List (moderate evidence)
Mendeliome v0.12237 OPN1MW Zornitza Stark Gene: opn1mw has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12236 OPN1LW Zornitza Stark Gene: opn1lw has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12234 BLOC1S6 Bryony Thompson Classified gene: BLOC1S6 as Green List (high evidence)
Mendeliome v0.12234 BLOC1S6 Bryony Thompson Gene: bloc1s6 has been classified as Green List (High Evidence).
Mendeliome v0.12231 OPN1LW Zornitza Stark Classified gene: OPN1LW as Amber List (moderate evidence)
Mendeliome v0.12231 OPN1LW Zornitza Stark Gene: opn1lw has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12230 SERPINA6 Zornitza Stark Gene: serpina6 has been classified as Green List (High Evidence).
Mendeliome v0.12227 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Green List (High Evidence).
Mendeliome v0.12227 SERPINA1 Zornitza Stark Phenotypes for gene: SERPINA1 were changed from to Emphysema due to AAT deficiency, MIM#613490; Emphysema-cirrhosis, due to AAT deficiency, MIM#613490; Hemorrhagic diathesis due to antithrombin Pittburgh, MIM#613490; alpha 1-antitrypsin deficiency, MONDO#0013282
Mendeliome v0.12224 OTOG Krithika Murali reviewed gene: OTOG: Rating: GREEN; Mode of pathogenicity: None; Publications: 29800624, 23122587; Phenotypes: Deafness, autosomal recessive 18B - MIM#614945; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12224 OSTM1 Krithika Murali reviewed gene: OSTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12627228, 15108279, 16813530, 23772242, 32048120; Phenotypes: Osteopetrosis, autosomal recessive 5 (MIM#259720); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12224 OSMR Krithika Murali reviewed gene: OSMR: Rating: GREEN; Mode of pathogenicity: None; Publications: 19375894, 19528426, 25054142, 20507362, 19690585; Phenotypes: Amyloidosis, primary localized cutaneous, 1 - MIM#105250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12224 SERPINA1 Samantha Ayres changed review comment from: Well established gene-disease relationship

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.; to: Well established gene-disease relationship

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.

MUTATIONAL & CLINICAL SPECTRUM
ZZ genotype: 2% have severe, neonatal/early-onset liver disease (potentially fatal/requiring liver transplantation), up to 6% have childhood onset liver disease. Also associated with adult-onset lung disease particularly emphysema (50%+ penetrance) - smoking is an important risk factor (close to 100% penetrance).

TREATMENT
There is no specific treatment for liver disease beyond transplant. There is treatment (AAT augmentation therapy) available to delay progression of lung disease phenotype.
Mendeliome v0.12224 SERPINA1 Samantha Ayres changed review comment from: Well established gene-disease association

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.; to: Well established gene-disease relationship

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.
Mendeliome v0.12224 SERPINA1 Samantha Ayres reviewed gene: SERPINA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301692, 9041988, 34408829; Phenotypes: Emphysema due to AAT deficiency, MIM#613490, Emphysema-cirrhosis, due to AAT deficiency, MIM#613490, Hemorrhagic diathesis due to antithrombin Pittburgh, MIM#613490, alpha 1-antitrypsin deficiency, MONDO#0013282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12224 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
Mendeliome v0.12221 TGM1 Zornitza Stark Gene: tgm1 has been classified as Green List (High Evidence).
Mendeliome v0.12221 TGM1 Zornitza Stark Phenotypes for gene: TGM1 were changed from to Ichthyosis, congenital, autosomal recessive 1, MIM#242300
Mendeliome v0.12218 TGM1 Zornitza Stark reviewed gene: TGM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890349, 24261627, 30302839; Phenotypes: Ichthyosis, congenital, autosomal recessive 1, MIM#242300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12218 TGM3 Zornitza Stark Gene: tgm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12215 TGM3 Zornitza Stark Classified gene: TGM3 as Amber List (moderate evidence)
Mendeliome v0.12215 TGM3 Zornitza Stark Gene: tgm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12214 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Mendeliome v0.12211 NUP93 Zornitza Stark Gene: nup93 has been classified as Green List (High Evidence).
Mendeliome v0.12208 NUP62 Zornitza Stark Gene: nup62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12205 NUP62 Zornitza Stark Classified gene: NUP62 as Amber List (moderate evidence)
Mendeliome v0.12205 NUP62 Zornitza Stark Gene: nup62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12204 ADH1B Zornitza Stark Gene: adh1b has been classified as Red List (Low Evidence).
Mendeliome v0.12203 CASP8 Zornitza Stark Gene: casp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12200 CASP8 Zornitza Stark Classified gene: CASP8 as Amber List (moderate evidence)
Mendeliome v0.12200 CASP8 Zornitza Stark Gene: casp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12198 ADCY3 Zornitza Stark Gene: adcy3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12198 ADCY3 Zornitza Stark Phenotypes for gene: ADCY3 were changed from to {Obesity, susceptibility to, BMIQ19} MIM#617885
Mendeliome v0.12195 ADCY3 Zornitza Stark Classified gene: ADCY3 as Amber List (moderate evidence)
Mendeliome v0.12195 ADCY3 Zornitza Stark Gene: adcy3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12194 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
Mendeliome v0.12191 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
Mendeliome v0.12189 TGFB1 Zornitza Stark Gene: tgfb1 has been classified as Green List (High Evidence).
Mendeliome v0.12186 TG Zornitza Stark Gene: tg has been classified as Green List (High Evidence).
Mendeliome v0.12186 TG Zornitza Stark Phenotypes for gene: TG were changed from to Thyroid dyshormonogenesis 3, MIM# 274700
Mendeliome v0.12183 TG Zornitza Stark reviewed gene: TG: Rating: GREEN; Mode of pathogenicity: None; Publications: 33832185, 19169491, 28620499, 18631008, 12915634; Phenotypes: Thyroid dyshormonogenesis 3, MIM# 274700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12181 ADRB1 Elena Savva Gene: adrb1 has been classified as Red List (Low Evidence).
Mendeliome v0.12181 ADRB1 Elena Savva Classified gene: ADRB1 as Red List (low evidence)
Mendeliome v0.12181 ADRB1 Elena Savva Gene: adrb1 has been classified as Red List (Low Evidence).
Mendeliome v0.12180 NTN1 Zornitza Stark Gene: ntn1 has been classified as Green List (High Evidence).
Mendeliome v0.12177 NSD1 Zornitza Stark Gene: nsd1 has been classified as Green List (High Evidence).
Mendeliome v0.12174 NRCAM Zornitza Stark Gene: nrcam has been classified as Green List (High Evidence).
Mendeliome v0.12174 NR4A3 Zornitza Stark Gene: nr4a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12174 NR4A3 Zornitza Stark Classified gene: NR4A3 as Red List (low evidence)
Mendeliome v0.12174 NR4A3 Zornitza Stark Gene: nr4a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12173 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Mendeliome v0.12169 NKX2-1 Zornitza Stark Gene: nkx2-1 has been classified as Green List (High Evidence).
Mendeliome v0.12169 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Mendeliome v0.12166 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Green List (High Evidence).
Mendeliome v0.12163 NDUFS4 Zornitza Stark Gene: ndufs4 has been classified as Green List (High Evidence).
Mendeliome v0.12160 NDUFV2 Zornitza Stark Gene: ndufv2 has been classified as Green List (High Evidence).
Mendeliome v0.12158 ADH1B Elena Savva Classified gene: ADH1B as Red List (low evidence)
Mendeliome v0.12158 ADH1B Elena Savva Gene: adh1b has been classified as Red List (Low Evidence).
Mendeliome v0.12154 CA2 Zornitza Stark Phenotypes for gene: CA2 were changed from to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730
Mendeliome v0.12152 CASP8 Ain Roesley changed review comment from: Boderline red/amber

1 family (the 2nd family reported in PMID:25814141 was found to be distantly related to the one in PMID:12353035)

Mice with targeted T cell and B cell caspase-8 deficiency present normal thymocyte development but a marked decrease in peripheral blood T-cells. Besides, when challenged with the lymphocytic choriomeningitis virus (LCMV), these animals showed a significantly impaired immune response to the infection that included impaired CD8 cell expansion and an abrogated ability to generate virus-specific CD8+ cytotoxic T-cells.; to: Borderline red/amber

1 family (the 2nd family reported in PMID:25814141 was found to be distantly related to the one in PMID:12353035)

Mice with targeted T cell and B cell caspase-8 deficiency present normal thymocyte development but a marked decrease in peripheral blood T-cells. Besides, when challenged with the lymphocytic choriomeningitis virus (LCMV), these animals showed a significantly impaired immune response to the infection that included impaired CD8 cell expansion and an abrogated ability to generate virus-specific CD8+ cytotoxic T-cells.
Mendeliome v0.12151 ADGRV1 Elena Savva Gene: adgrv1 has been classified as Green List (High Evidence).
Mendeliome v0.12150 ADCY3 Elena Savva reviewed gene: ADCY3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11055432, 29311636, 29311637; Phenotypes: {Obesity, susceptibility to, BMIQ19} MIM#617885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12149 CASP10 Ain Roesley Gene: casp10 has been classified as Green List (High Evidence).
Mendeliome v0.12148 NUBPL Zornitza Stark Gene: nubpl has been classified as Green List (High Evidence).
Mendeliome v0.12145 NTRK1 Zornitza Stark Gene: ntrk1 has been classified as Green List (High Evidence).
Mendeliome v0.12145 NTRK1 Zornitza Stark Phenotypes for gene: NTRK1 were changed from to Insensitivity to pain, congenital, with anhidrosis - MIM#256800
Mendeliome v0.12142 NTF4 Zornitza Stark Gene: ntf4 has been classified as Red List (Low Evidence).
Mendeliome v0.12139 CASK Ain Roesley Phenotypes for gene: CASK were changed from FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422 to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422
Mendeliome v0.12139 NTF4 Zornitza Stark Classified gene: NTF4 as Red List (low evidence)
Mendeliome v0.12139 NTF4 Zornitza Stark Gene: ntf4 has been classified as Red List (Low Evidence).
Mendeliome v0.12138 CASK Ain Roesley Phenotypes for gene: CASK were changed from to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422
Mendeliome v0.12137 CASK Ain Roesley Gene: cask has been classified as Green List (High Evidence).
Mendeliome v0.12137 CASK Ain Roesley Gene: cask has been classified as Green List (High Evidence).
Mendeliome v0.12135 NSUN2 Zornitza Stark Gene: nsun2 has been classified as Green List (High Evidence).
Mendeliome v0.12135 NSUN2 Zornitza Stark Phenotypes for gene: NSUN2 were changed from to Mental retardation, autosomal recessive 5 - MIM#611091
Mendeliome v0.12134 CASK Ain Roesley reviewed gene: CASK: Rating: GREEN; Mode of pathogenicity: None; Publications: 24278995; Phenotypes: FG syndrome 4 MIM#300422, Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749, Mental retardation, with or without nystagmus MIM#300422; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.12132 NSUN2 Zornitza Stark reviewed gene: NSUN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22541559, 22541562, 21063731, 22577224, 35126837; Phenotypes: Mental retardation, autosomal recessive 5 - MIM#611091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12132 NRXN1 Zornitza Stark Gene: nrxn1 has been classified as Green List (High Evidence).
Mendeliome v0.12129 CARD11 Ain Roesley Phenotypes for gene: CARD11 were changed from Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638 to Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638
Mendeliome v0.12128 CARD11 Ain Roesley Phenotypes for gene: CARD11 were changed from to Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638
Mendeliome v0.12128 CARD11 Ain Roesley Gene: card11 has been classified as Green List (High Evidence).
Mendeliome v0.12127 CARD11 Ain Roesley reviewed gene: CARD11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561803, 12818158, 23374270, 28628108; Phenotypes: Immunodeficiency 11A, autosomal recessive, MIM# 615206, Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12127 CALM3 Ain Roesley Gene: calm3 has been classified as Green List (High Evidence).
Mendeliome v0.12126 CALM2 Ain Roesley Gene: calm2 has been classified as Green List (High Evidence).
Mendeliome v0.12124 CALM1 Ain Roesley Gene: calm1 has been classified as Green List (High Evidence).
Mendeliome v0.12122 NRL Zornitza Stark Gene: nrl has been classified as Green List (High Evidence).
Mendeliome v0.12122 NRL Zornitza Stark Phenotypes for gene: NRL were changed from to Retinitis pigmentosa 27 - MIM#613750; Retinal degeneration, autosomal recessive, clumped pigment type
Mendeliome v0.12118 CACNA2D4 Ain Roesley Gene: cacna2d4 has been classified as Green List (High Evidence).
Mendeliome v0.12117 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Mendeliome v0.12115 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Mendeliome v0.12112 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Mendeliome v0.12109 SCP2 Zornitza Stark Gene: scp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12108 SCP2 Zornitza Stark Classified gene: SCP2 as Amber List (moderate evidence)
Mendeliome v0.12108 SCP2 Zornitza Stark Gene: scp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12103 CACNA2D2 Ain Roesley Gene: cacna2d2 has been classified as Green List (High Evidence).
Mendeliome v0.12102 SCP2 Zornitza Stark Classified gene: SCP2 as Red List (low evidence)
Mendeliome v0.12102 SCP2 Zornitza Stark Gene: scp2 has been classified as Red List (Low Evidence).
Mendeliome v0.12099 CACNA1F Ain Roesley Gene: cacna1f has been classified as Green List (High Evidence).
Mendeliome v0.12099 TUBB1 Zornitza Stark Gene: tubb1 has been classified as Green List (High Evidence).
Mendeliome v0.12096 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Green List (High Evidence).
Mendeliome v0.12096 SCARB2 Zornitza Stark Phenotypes for gene: SCARB2 were changed from to Progressive Myoclonus Epilepsy, MONDO:0020074; Epilepsy, progressive myoclonic 4, with or without renal failure, MIM #254900
Mendeliome v0.12093 SASH1 Zornitza Stark Gene: sash1 has been classified as Green List (High Evidence).
Mendeliome v0.12093 SASH1 Zornitza Stark Phenotypes for gene: SASH1 were changed from to Dyschromatosis universalis hereditaria 1, MIM #127500; familial generalized lentiginosis MONDO:007891
Mendeliome v0.12090 SASH1 Zornitza Stark reviewed gene: SASH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyschromatosis universalis hereditaria 1, MIM# 127500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12090 CABP2 Ain Roesley Gene: cabp2 has been classified as Green List (High Evidence).
Mendeliome v0.12090 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Green List (High Evidence).
Mendeliome v0.12090 CABP2 Ain Roesley Phenotypes for gene: CABP2 were changed from to Deafness, autosomal recessive 93, MIM# 614899
Mendeliome v0.12090 TUBB4B Zornitza Stark Phenotypes for gene: TUBB4B were changed from to Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879; MONDO:0060650
Mendeliome v0.12089 CABP2 Ain Roesley reviewed gene: CABP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22981119, 31661684, 28183797; Phenotypes: Deafness, autosomal recessive 93, MIM# 614899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12088 TUBB4B Zornitza Stark reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 35240325; Phenotypes: Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879, MONDO:0060650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12086 TUFM Zornitza Stark Gene: tufm has been classified as Green List (High Evidence).
Mendeliome v0.12083 CA2 Ain Roesley Gene: ca2 has been classified as Green List (High Evidence).
Mendeliome v0.12083 CA2 Ain Roesley reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34624559, 33555497, 12566520, 7627193; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12082 CA12 Ain Roesley Gene: ca12 has been classified as Green List (High Evidence).
Mendeliome v0.12082 CA12 Ain Roesley Phenotypes for gene: CA12 were changed from to Hyperchlorhidrosis, isolated MIM#143860
Mendeliome v0.12080 NR2E3 Zornitza Stark Gene: nr2e3 has been classified as Green List (High Evidence).
Mendeliome v0.12080 CA12 Ain Roesley reviewed gene: CA12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21035102, 21184099, 26911677; Phenotypes: Hyperchlorhidrosis, isolated MIM#143860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12077 NR0B2 Zornitza Stark Gene: nr0b2 has been classified as Red List (Low Evidence).
Mendeliome v0.12076 NR0B2 Zornitza Stark Phenotypes for gene: NR0B2 were changed from to Obesity, mild, early-onset, MIM# 601665
Mendeliome v0.12075 NR0B2 Zornitza Stark Classified gene: NR0B2 as Red List (low evidence)
Mendeliome v0.12075 NR0B2 Zornitza Stark Gene: nr0b2 has been classified as Red List (Low Evidence).
Mendeliome v0.12074 NPSR1 Zornitza Stark Gene: npsr1 has been classified as Red List (Low Evidence).
Mendeliome v0.12072 NPSR1 Zornitza Stark Classified gene: NPSR1 as Red List (low evidence)
Mendeliome v0.12072 NPSR1 Zornitza Stark Gene: npsr1 has been classified as Red List (Low Evidence).
Mendeliome v0.12071 ACER3 Zornitza Stark edited their review of gene: ACER3: Added comment: Additional publication (Dehvani et al., 2021; PMID: 34281620) detailing three further unrelated cases, each with novel homozygous variants in the ACER3 gene. All individuals displayed features of progressive leukoencephalopathy, developmental delay, hypotonia, appendicular spasticity, and dystonia. Early development is apparently normal followed by symptoms of stagnation and neurologic regression (onset within first year of life).; Changed rating: GREEN; Changed publications: 32816236, 26792856, 34281620; Changed phenotypes: Leukodystrophy, progressive, early childhood-onset, MIM:617762
Mendeliome v0.12071 LIAS Alison Yeung Gene: lias has been classified as Green List (High Evidence).
Mendeliome v0.12071 LIAS Alison Yeung Phenotypes for gene: LIAS were changed from to Hyperglycinemia, lactic acidosis, and seizures, MIM# 614462
Mendeliome v0.12068 LIAS Alison Yeung reviewed gene: LIAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152680, 24334290, 26108146; Phenotypes: Hyperglycinemia, lactic acidosis, and seizures, MIM# 614462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12067 LHX4 Alison Yeung Gene: lhx4 has been classified as Green List (High Evidence).
Mendeliome v0.12066 LHX3 Alison Yeung Gene: lhx3 has been classified as Green List (High Evidence).
Mendeliome v0.12064 LHB Alison Yeung Gene: lhb has been classified as Green List (High Evidence).
Mendeliome v0.12062 SCARB2 Samantha Ayres reviewed gene: SCARB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18308289, 18424452, 23659519, 19847901, 18022370, 19933215; Phenotypes: Progressive Myoclonus Epilepsy, MONDO:0020074, Epilepsy, progressive myoclonic 4, with or without renal failure, MIM #254900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12062 SASH1 Samantha Ayres reviewed gene: SASH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23333244, 27885802, 32981204; Phenotypes: Dyschromatosis universalis hereditaria 1, MIM #127500, familial generalized lentiginosis MONDO:007891; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.12062 TUBB4B Manny Jacobs reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29198720; Phenotypes: Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879, MONDO:0060650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12062 LGI1 Alison Yeung Gene: lgi1 has been classified as Green List (High Evidence).
Mendeliome v0.12059 NTRK1 Krithika Murali reviewed gene: NTRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10233776, 19250380, 10861667, 10982191, 20301726, 20089052; Phenotypes: Insensitivity to pain, congenital, with anhidrosis - MIM#256800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12059 LEMD3 Alison Yeung Gene: lemd3 has been classified as Green List (High Evidence).
Mendeliome v0.12059 LEMD3 Alison Yeung Phenotypes for gene: LEMD3 were changed from to Buschke-Ollendorff syndrome MIM#166700; Osteopoikilosis with or without melorheostosis MIM#166700
Mendeliome v0.12056 NRL Krithika Murali reviewed gene: NRL: Rating: GREEN; Mode of pathogenicity: None; Publications: 15591106, 29385733, 21981118, 10192380, 9344665; Phenotypes: Retinitis pigmentosa 27 - MIM#613750, Retinal degeneration, autosomal recessive, clumped pigment type; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12056 LDLRAP1 Alison Yeung Gene: ldlrap1 has been classified as Green List (High Evidence).
Mendeliome v0.12053 LDHB Alison Yeung Gene: ldhb has been classified as Red List (Low Evidence).
Mendeliome v0.12050 LDHB Alison Yeung Classified gene: LDHB as Red List (low evidence)
Mendeliome v0.12050 LDHB Alison Yeung Added comment: Comment on list classification: Not associated with clinical disease
Mendeliome v0.12050 LDHB Alison Yeung Gene: ldhb has been classified as Red List (Low Evidence).
Mendeliome v0.12049 LCAT Alison Yeung Gene: lcat has been classified as Green List (High Evidence).
Mendeliome v0.12046 LCA5 Alison Yeung Gene: lca5 has been classified as Green List (High Evidence).
Mendeliome v0.12046 LCA5 Alison Yeung Phenotypes for gene: LCA5 were changed from to Leber Congenital Amaurosis 5, MIM# 604537
Mendeliome v0.12043 LCA5 Alison Yeung reviewed gene: LCA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 17546029; Phenotypes: Leber Congenital Amaurosis 5, MIM# 604537; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12043 MSMB Zornitza Stark Gene: msmb has been classified as Red List (Low Evidence).
Mendeliome v0.12041 MSMB Zornitza Stark Classified gene: MSMB as Red List (low evidence)
Mendeliome v0.12041 MSMB Zornitza Stark Gene: msmb has been classified as Red List (Low Evidence).
Mendeliome v0.12040 SON Zornitza Stark Gene: son has been classified as Green List (High Evidence).
Mendeliome v0.12037 SNX3 Zornitza Stark Gene: snx3 has been classified as Red List (Low Evidence).
Mendeliome v0.12037 SNX3 Zornitza Stark Classified gene: SNX3 as Red List (low evidence)
Mendeliome v0.12037 SNX3 Zornitza Stark Gene: snx3 has been classified as Red List (Low Evidence).
Mendeliome v0.12036 SMARCE1 Zornitza Stark Phenotypes for gene: SMARCE1 were changed from Coffin-Siris syndrome 5, MIM# 616938 to Coffin-Siris syndrome 5, MIM# 616938; {Meningioma, familial, susceptibility to} 607174
Mendeliome v0.12035 SMARCE1 Zornitza Stark changed review comment from: Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly.

Accounts for ~2% of Coffin Siris syndrome.; to: Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly.

Accounts for ~2% of Coffin Siris syndrome.

Germline LoF variants also linked to familial meningioma.
Mendeliome v0.12035 SMARCE1 Zornitza Stark edited their review of gene: SMARCE1: Changed publications: 23377182, 22426308, 23906836, 23929686, 32732226, 32436246, 32410215, 34205270; Changed phenotypes: Coffin-Siris syndrome 5, MIM# 616938, {Meningioma, familial, susceptibility to} 607174
Mendeliome v0.12034 SMARCE1 Zornitza Stark Gene: smarce1 has been classified as Green List (High Evidence).
Mendeliome v0.12034 SMARCE1 Zornitza Stark Phenotypes for gene: SMARCE1 were changed from to Coffin-Siris syndrome 5, MIM# 616938
Mendeliome v0.12031 SMARCE1 Zornitza Stark reviewed gene: SMARCE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308, 23906836, 23929686, 32732226, 32436246, 32410215, 34205270; Phenotypes: Coffin-Siris syndrome 5, MIM# 616938; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12031 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Mendeliome v0.12028 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Mendeliome v0.12028 MAT1A Zornitza Stark Phenotypes for gene: MAT1A were changed from to Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency MIM#250850; Methionine adenosyltransferase deficiency, autosomal recessive MIM#250850; Disorders of the metabolism of sulphur amino acids
Mendeliome v0.12025 SNX14 Zornitza Stark Gene: snx14 has been classified as Green List (High Evidence).
Mendeliome v0.12025 SNX14 Zornitza Stark Phenotypes for gene: SNX14 were changed from to Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354)
Mendeliome v0.12022 SNX14 Zornitza Stark reviewed gene: SNX14: Rating: GREEN; Mode of pathogenicity: None; Publications: 25439728, 25848753, 27913285; Phenotypes: Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12022 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Mendeliome v0.12019 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Mendeliome v0.12019 SNAP29 Zornitza Stark Phenotypes for gene: SNAP29 were changed from to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, MIM#609528
Mendeliome v0.12016 SNAP29 Zornitza Stark reviewed gene: SNAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: 29051910, 21073448, 30793783; Phenotypes: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, MIM#609528; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12016 SNAP25 Zornitza Stark Gene: snap25 has been classified as Green List (High Evidence).
Mendeliome v0.12013 SNAI2 Zornitza Stark Gene: snai2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12010 SNAI2 Zornitza Stark Classified gene: SNAI2 as Amber List (moderate evidence)
Mendeliome v0.12010 SNAI2 Zornitza Stark Gene: snai2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12009 SMS Zornitza Stark Gene: sms has been classified as Green List (High Evidence).
Mendeliome v0.12006 GRIN1 Zornitza Stark Phenotypes for gene: GRIN1 were changed from 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 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 v0.12005 GRIN1 Zornitza Stark edited their review of gene: GRIN1: Changed phenotypes: 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 v0.12005 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
Mendeliome v0.12002 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Mendeliome v0.12002 ROBO3 Zornitza Stark Phenotypes for gene: ROBO3 were changed from to Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM# 607313)
Mendeliome v0.11999 ROBO2 Zornitza Stark Gene: robo2 has been classified as Green List (High Evidence).
Mendeliome v0.11999 ROBO2 Zornitza Stark Phenotypes for gene: ROBO2 were changed from to Vesicoureteral reflux 2 - MIM#610878; CAKUT
Mendeliome v0.11996 ROBO2 Zornitza Stark reviewed gene: ROBO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18235093, 19350278, 24429398, 17357069, 26026792, 29194579, 34059960; Phenotypes: Vesicoureteral reflux 2 - MIM#610878, CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11996 RNF216 Zornitza Stark Gene: rnf216 has been classified as Green List (High Evidence).
Mendeliome v0.11993 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Mendeliome v0.11993 ATP2B2 Zornitza Stark Phenotypes for gene: ATP2B2 were changed from progressive sensorineural deafness to Deafness, autosomal dominant 82, MIM# 619804; {Deafness, autosomal recessive 12, modifier of}, MIM# 601386
Mendeliome v0.11991 ATP2B2 Zornitza Stark edited their review of gene: ATP2B2: Changed phenotypes: Deafness, autosomal dominant 82, MIM# 619804, {Deafness, autosomal recessive 12, modifier of}, MIM# 601386
Mendeliome v0.11991 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Mendeliome v0.11990 TFAP2B Zornitza Stark changed review comment from: Well established association with syndromic and non-syndromic PDA.; to: Well established association with syndromic and non-syndromic PDA.

Four individuals reported in PMID: 31292255 (Correction in PMID: 31405973) as part of a craniosynostosis cohort: 2 de novo and 2 inherited. There is evidence for reduced penetrance as in one case the variant was inherited from an unaffected parent (affected parent for the other inherited variant).
Mendeliome v0.11990 TFAP2B Zornitza Stark edited their review of gene: TFAP2B: Changed publications: 31292255, 11505339, 15684060, 18752453, 21643846; Changed phenotypes: Char syndrome, MIM# 169100, Patent ductus arteriosus 2, MIM# 617035, Syndromic craniosynostosis
Mendeliome v0.11990 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035 to Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035; Syndromic craniosynostosis
Mendeliome v0.11986 TERT Zornitza Stark Gene: tert has been classified as Green List (High Evidence).
Mendeliome v0.11986 TERT Zornitza Stark Phenotypes for gene: TERT were changed from to Dyskeratosis congenita, MIM# 613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, MIM# 614742
Mendeliome v0.11983 TERT Zornitza Stark reviewed gene: TERT: Rating: GREEN; Mode of pathogenicity: None; Publications: 16247010, 15814878; Phenotypes: Dyskeratosis congenita, MIM# 613989, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, MIM# 614742; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11983 TERC Zornitza Stark Gene: terc has been classified as Green List (High Evidence).
Mendeliome v0.11983 TERC Zornitza Stark Phenotypes for gene: TERC were changed from to Dyskeratosis congenita, autosomal dominant 1, MIM# 127550
Mendeliome v0.11980 TERC Zornitza Stark reviewed gene: TERC: Rating: GREEN; Mode of pathogenicity: None; Publications: 11574891; Phenotypes: Dyskeratosis congenita, autosomal dominant 1, MIM# 127550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11980 TEK Zornitza Stark Gene: tek has been classified as Green List (High Evidence).
Mendeliome v0.11977 TEAD1 Zornitza Stark Gene: tead1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11975 TEAD1 Zornitza Stark changed review comment from: Sveinsson chorioretinal atrophy (SCRA) is characterized by bilateral, well-defined, tongue-shaped strips of atrophic retina and choroid that extend from the optic nerve into the peripheral ocular fundus. The lesions may be evident at birth and usually progress at a variable rate, sometimes leading to central visual loss. Separate small distinct circular atrophic lesions are observed in the peripheral ocular fundus in some patients. Congenital anterior polar cataracts are found in approximately 25% of affected individuals.

The vast majority of reported cases were of Icelandic origin but the characteristic clinical picture of SCRA is also described in patients of non-Icelandic descent. The variant reported in the Icelanding population is (c.1261T>C, p.Tyr421His), another variant at same position c.1261T>A, p.Tyr421Asn also reported in non-Icelandic family.

Functional data supports gene-disease association.; to: Sveinsson chorioretinal atrophy (SCRA) is characterized by bilateral, well-defined, tongue-shaped strips of atrophic retina and choroid that extend from the optic nerve into the peripheral ocular fundus. The lesions may be evident at birth and usually progress at a variable rate, sometimes leading to central visual loss. Separate small distinct circular atrophic lesions are observed in the peripheral ocular fundus in some patients. Congenital anterior polar cataracts are found in approximately 25% of affected individuals.

The vast majority of reported cases were of Icelandic origin but the characteristic clinical picture of SCRA is also described in patients of non-Icelandic descent. The variant reported in the Icelanding population is (c.1261T>C, p.Tyr421His), another variant at same position c.1261T>A, p.Tyr421Asn also reported in non-Icelandic family.

A de novo nonsense variant has also been reported in a case with Aicardi syndrome with infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae.
Mendeliome v0.11975 TEAD1 Zornitza Stark Classified gene: TEAD1 as Amber List (moderate evidence)
Mendeliome v0.11975 TEAD1 Zornitza Stark Gene: tead1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11973 TDP1 Zornitza Stark Phenotypes for gene: TDP1 were changed from to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 , MIM# 607250
Mendeliome v0.11970 TDP1 Zornitza Stark Classified gene: TDP1 as Amber List (moderate evidence)
Mendeliome v0.11970 TDP1 Zornitza Stark Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11969 TDP1 Zornitza Stark reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31182267, 12244316; Phenotypes: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 , MIM# 607250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11969 TCIRG1 Zornitza Stark Gene: tcirg1 has been classified as Green List (High Evidence).
Mendeliome v0.11969 TCIRG1 Zornitza Stark Phenotypes for gene: TCIRG1 were changed from to Osteopetrosis, autosomal recessive 1, MIM# 259700
Mendeliome v0.11966 TCIRG1 Zornitza Stark reviewed gene: TCIRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34624559, 34210262, 30084437, 28816234; Phenotypes: Osteopetrosis, autosomal recessive 1, MIM# 259700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11966 TCF4 Zornitza Stark Gene: tcf4 has been classified as Green List (High Evidence).
Mendeliome v0.11963 TCAP Zornitza Stark Gene: tcap has been classified as Green List (High Evidence).
Mendeliome v0.11963 TCAP Zornitza Stark Phenotypes for gene: TCAP were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 7, MIM# 601954
Mendeliome v0.11961 TCAP Zornitza Stark reviewed gene: TCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 7, MIM# 601954; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11961 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Mendeliome v0.11958 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Mendeliome v0.11955 TBL1XR1 Zornitza Stark Gene: tbl1xr1 has been classified as Green List (High Evidence).
Mendeliome v0.11952 TBCK Zornitza Stark Gene: tbck has been classified as Green List (High Evidence).
Mendeliome v0.11949 TBC1D23 Zornitza Stark Gene: tbc1d23 has been classified as Green List (High Evidence).
Mendeliome v0.11949 TBC1D23 Zornitza Stark Phenotypes for gene: TBC1D23 were changed from to Pontocerebellar hypoplasia, type 11, MIM# 617695
Mendeliome v0.11946 TBC1D1 Zornitza Stark Gene: tbc1d1 has been classified as Green List (High Evidence).
Mendeliome v0.11943 TAZ Zornitza Stark Gene: taz has been classified as Green List (High Evidence).
Mendeliome v0.11941 TAT Zornitza Stark Phenotypes for gene: TAT were changed from Tyrosinemia, type II, MIM# 276600 to Tyrosinaemia, type II, MIM# 276600
Mendeliome v0.11940 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Mendeliome v0.11940 TAT Zornitza Stark Phenotypes for gene: TAT were changed from to Tyrosinemia, type II, MIM# 276600
Mendeliome v0.11938 TAS2R38 Zornitza Stark Gene: tas2r38 has been classified as Red List (Low Evidence).
Mendeliome v0.11936 TAS2R38 Zornitza Stark Classified gene: TAS2R38 as Red List (low evidence)
Mendeliome v0.11936 TAS2R38 Zornitza Stark Gene: tas2r38 has been classified as Red List (Low Evidence).
Mendeliome v0.11935 TAS2R16 Zornitza Stark Gene: tas2r16 has been classified as Red List (Low Evidence).
Mendeliome v0.11935 TAS2R16 Zornitza Stark Phenotypes for gene: TAS2R16 were changed from to [Beta-glycopyranoside tasting], (3) {Alcohol dependence, susceptibility to} 617956
Mendeliome v0.11933 TAS2R16 Zornitza Stark Classified gene: TAS2R16 as Red List (low evidence)
Mendeliome v0.11933 TAS2R16 Zornitza Stark Gene: tas2r16 has been classified as Red List (Low Evidence).
Mendeliome v0.11932 TAS2R16 Zornitza Stark reviewed gene: TAS2R16: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Beta-glycopyranoside tasting], (3) {Alcohol dependence, susceptibility to} 617956; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11932 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Mendeliome v0.11932 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
Mendeliome v0.11929 TANGO2 Zornitza Stark reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26805782, 30245509; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11929 TACR3 Zornitza Stark Gene: tacr3 has been classified as Green List (High Evidence).
Mendeliome v0.11926 TAC3 Zornitza Stark Gene: tac3 has been classified as Green List (High Evidence).
Mendeliome v0.11923 T Zornitza Stark Gene: t has been classified as Red List (Low Evidence).
Mendeliome v0.11923 T Zornitza Stark Phenotypes for gene: T were changed from to Sacral agenesis with vertebral anomalies, MIM# 615709
Mendeliome v0.11920 T Zornitza Stark Classified gene: T as Red List (low evidence)
Mendeliome v0.11920 T Zornitza Stark Gene: t has been classified as Red List (Low Evidence).
Mendeliome v0.11919 T Zornitza Stark reviewed gene: T: Rating: RED; Mode of pathogenicity: None; Publications: 24253444, 28116192; Phenotypes: Sacral agenesis with vertebral anomalies 615709; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11911 LBR Alison Yeung Phenotypes for gene: LBR were changed from to Greenberg skeletal dysplasia, MIM# 215140
Mendeliome v0.11910 LBR Alison Yeung Gene: lbr has been classified as Green List (High Evidence).
Mendeliome v0.11908 LAT Alison Yeung Gene: lat has been classified as Green List (High Evidence).
Mendeliome v0.11903 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from Hydrocephalus due to aqueductal stenosis, MIM# 307000; MASA syndrome, MIM# 303350; L1 syndrome, MONDO:0017140 to Hydrocephalus due to aqueductal stenosis, MIM# 307000; MASA syndrome, MIM# 303350; L1 syndrome, MONDO:0017140; Corpus callosum, partial agenesis of, MIM# 304100
Mendeliome v0.11902 L1CAM Zornitza Stark reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrocephalus due to aqueductal stenosis, MIM# 307000, Corpus callosum, partial agenesis of, MIM# 304100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11900 NPRL3 Zornitza Stark Gene: nprl3 has been classified as Green List (High Evidence).
Mendeliome v0.11897 NPPC Zornitza Stark Gene: nppc has been classified as Red List (Low Evidence).
Mendeliome v0.11894 NPPC Zornitza Stark Classified gene: NPPC as Red List (low evidence)
Mendeliome v0.11894 NPPC Zornitza Stark Gene: nppc has been classified as Red List (Low Evidence).
Mendeliome v0.11893 NOTCH2 Zornitza Stark Gene: notch2 has been classified as Green List (High Evidence).
Mendeliome v0.11890 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Mendeliome v0.11887 NONO Zornitza Stark Gene: nono has been classified as Green List (High Evidence).
Mendeliome v0.11884 NOL3 Zornitza Stark Gene: nol3 has been classified as Red List (Low Evidence).
Mendeliome v0.11881 NOL3 Zornitza Stark Classified gene: NOL3 as Red List (low evidence)
Mendeliome v0.11881 NOL3 Zornitza Stark Gene: nol3 has been classified as Red List (Low Evidence).
Mendeliome v0.11880 NOG Zornitza Stark Gene: nog has been classified as Green List (High Evidence).
Mendeliome v0.11880 NOG Zornitza Stark Phenotypes for gene: NOG were changed from to 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)
Mendeliome v0.11877 NNT Zornitza Stark Gene: nnt has been classified as Green List (High Evidence).
Mendeliome v0.11874 NLRP7 Zornitza Stark Gene: nlrp7 has been classified as Green List (High Evidence).
Mendeliome v0.11871 NLRP12 Zornitza Stark Gene: nlrp12 has been classified as Green List (High Evidence).
Mendeliome v0.11868 LAS1L Alison Yeung Gene: las1l has been classified as Green List (High Evidence).