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Date Panel Item Activity
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Mendeliome v1.4865 ASTN2 Lucy Spencer reviewed gene: ASTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28940097, 34412080, 24381304, 32094338, 38674362; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, ASTN2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Fibrosis_Interstitial Lung Disease v1.12 Sarah Milton Copied Region FOXF1 upstream regulatory region from panel Mendeliome
Pulmonary Fibrosis_Interstitial Lung Disease v1.12 FOXF1 upstream regulatory region Sarah Milton Region: FOXF1 upstream regulatory region was added
Region: FOXF1 upstream regulatory region was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: FOXF1 upstream regulatory region.
Mode of inheritance for Region: FOXF1 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: FOXF1 upstream regulatory region were set to PMID: 27822317, 27071622, 23034409, 24842713
Phenotypes for Region: FOXF1 upstream regulatory region were set to Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380
Intellectual disability syndromic and non-syndromic v1.784 ISCA-37448-Loss Sarah Milton Classified Region: ISCA-37448-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.784 ISCA-37448-Loss Sarah Milton Region: isca-37448-loss has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.157 ISCA-37494-Loss Sarah Milton Classified Region: ISCA-37494-Loss as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.157 ISCA-37494-Loss Sarah Milton Region: isca-37494-loss has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.783 ISCA-37498-Loss Sarah Milton Classified Region: ISCA-37498-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.783 ISCA-37498-Loss Sarah Milton Region: isca-37498-loss has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.782 ISCA-37498-Loss Sarah Milton Classified Region: ISCA-37498-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.782 ISCA-37498-Loss Sarah Milton Region: isca-37498-loss has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.782 ISCA-37498-Loss Sarah Milton Classified Region: ISCA-37498-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.782 ISCA-37498-Loss Sarah Milton Region: isca-37498-loss has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.362 Sarah Milton Copied Region POU3F4 upstream regulatory region from panel Mendeliome
Deafness_IsolatedAndComplex v1.362 POU3F4 upstream regulatory region Sarah Milton Region: POU3F4 upstream regulatory region was added
Region: POU3F4 upstream regulatory region was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: POU3F4 upstream regulatory region.
Mode of inheritance for Region: POU3F4 upstream regulatory region was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for Region: POU3F4 upstream regulatory region were set to PMID: 41170199, 35189936, 33860785
Phenotypes for Region: POU3F4 upstream regulatory region were set to Deafness, X-linked 2 MIM#304400
Intellectual disability syndromic and non-syndromic v1.781 ISCA-46296-Loss Sarah Milton Classified Region: ISCA-46296-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.781 ISCA-46296-Loss Sarah Milton Region: isca-46296-loss has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.781 ISCA-46296-Loss Sarah Milton Classified Region: ISCA-46296-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.781 ISCA-46296-Loss Sarah Milton Region: isca-46296-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.164 ISCA-46302-Gain Sarah Milton Classified Region: ISCA-46302-Gain as Green List (high evidence)
Common deletion and duplication syndromes v0.164 ISCA-46302-Gain Sarah Milton Region: isca-46302-gain has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.163 ISCA-46300-Loss Sarah Milton Classified Region: ISCA-46300-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.163 ISCA-46300-Loss Sarah Milton Region: isca-46300-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.162 ISCA-46296-Loss Sarah Milton Classified Region: ISCA-46296-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.162 ISCA-46296-Loss Sarah Milton Region: isca-46296-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.161 ISCA-37498-Loss Sarah Milton Classified Region: ISCA-37498-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.161 ISCA-37498-Loss Sarah Milton Region: isca-37498-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.160 ISCA-37494-Loss Sarah Milton Classified Region: ISCA-37494-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.160 ISCA-37494-Loss Sarah Milton Region: isca-37494-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.159 ISCA-37448-Loss Sarah Milton Classified Region: ISCA-37448-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.159 ISCA-37448-Loss Sarah Milton Region: isca-37448-loss has been classified as Green List (High Evidence).
Differences of Sex Development v1.56 SOX9 upstream regulatory region gain Sarah Milton Classified Region: SOX9 upstream regulatory region gain as Green List (high evidence)
Differences of Sex Development v1.56 SOX9 upstream regulatory region gain Sarah Milton Region: sox9 upstream regulatory region gain has been classified as Green List (High Evidence).
Mendeliome v1.4865 SOX9 upstream regulatory region gain Sarah Milton Classified Region: SOX9 upstream regulatory region gain as Green List (high evidence)
Mendeliome v1.4865 SOX9 upstream regulatory region gain Sarah Milton Region: sox9 upstream regulatory region gain has been classified as Green List (High Evidence).
Skeletal dysplasia v0.449 SHOX downstream regulatory region Sarah Milton Classified Region: SHOX downstream regulatory region as Green List (high evidence)
Skeletal dysplasia v0.449 SHOX downstream regulatory region Sarah Milton Region: shox downstream regulatory region has been classified as Green List (High Evidence).
Radial Ray Abnormalities v1.23 SHOX downstream regulatory region Sarah Milton Classified Region: SHOX downstream regulatory region as Green List (high evidence)
Radial Ray Abnormalities v1.23 SHOX downstream regulatory region Sarah Milton Region: shox downstream regulatory region has been classified as Green List (High Evidence).
Growth failure v1.108 SHOX downstream regulatory region Sarah Milton Classified Region: SHOX downstream regulatory region as Green List (high evidence)
Growth failure v1.108 SHOX downstream regulatory region Sarah Milton Region: shox downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4864 SHOX downstream regulatory region Sarah Milton Classified Region: SHOX downstream regulatory region as Green List (high evidence)
Mendeliome v1.4864 SHOX downstream regulatory region Sarah Milton Region: shox downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Classified Region: POU3F4 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Added comment: Comment on list classification: Well established with specific temporal bone findings
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Region: pou3f4 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Classified Region: POU3F4 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Added comment: Comment on list classification: Well established with specific temporal bone findings
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Region: pou3f4 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4862 POU3F4 upstream regulatory region Sarah Milton changed review comment from: POU3F4 encodes POU domain, class III, transcriptional factor 4, a transcription factor with functional targets not fully elucidated but known to affect expression of GJB6, EPHA4 and EFNB2 in development.

17 patients reported across a number of publications with deletions sized between 8kb to 1.74mb upstream of POU3F4 presented with X linked deafness.

Yang et al PMID: 41170199 reported 4 male individuals from one pedigree with deafness segregating with the upstream deletion.
qPCR demonstrated reduced mRNA expression of POU3F4 in two affected males with the deletion with normal levels in their unaffected father.

It is proposed this deletion is removing an upstream enhancer element however functional studies have not been performed to demonstrate this as of yet.

The coordinates used in this entry are the largest reported to cause the phenotype most deletions reported in affected individuals were smaller.
Sources: Literature; to: POU3F4 encodes POU domain, class III, transcriptional factor 4, a transcription factor with functional targets not fully elucidated but known to affect expression of GJB6, EPHA4 and EFNB2 in development.

17 patients reported across a number of publications with deletions sized between 8kb to 1.74mb upstream of POU3F4 presented with X linked deafness - mixed conductive and sensorineural. A typical temporal bone deformity is often seen that includes dilatation of the inner auditory canal and a fistulous connection between the internal auditory canal and the cochlear basal turn.

Yang et al PMID: 41170199 reported 4 male individuals from one pedigree with deafness segregating with the upstream deletion.
qPCR demonstrated reduced mRNA expression of POU3F4 in two affected males with the deletion with normal levels in their unaffected father.

It is proposed this deletion is removing an upstream enhancer element however this has not been clearly demonstrated yet.

The coordinates used in this entry are the largest reported to cause the phenotype most deletions reported in affected individuals were smaller.
Sources: Literature
Glaucoma congenital v1.13 PITX2 upstream regulatory region Sarah Milton Classified Region: PITX2 upstream regulatory region as Green List (high evidence)
Glaucoma congenital v1.13 PITX2 upstream regulatory region Sarah Milton Region: pitx2 upstream regulatory region has been classified as Green List (High Evidence).
Glaucoma congenital v1.13 PITX2 upstream regulatory region Sarah Milton Classified Region: PITX2 upstream regulatory region as Green List (high evidence)
Glaucoma congenital v1.13 PITX2 upstream regulatory region Sarah Milton Region: pitx2 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4862 PITX2 upstream regulatory region Sarah Milton Classified Region: PITX2 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4862 PITX2 upstream regulatory region Sarah Milton Region: pitx2 upstream regulatory region has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.22 PITX2 upstream regulatory region Sarah Milton Classified Region: PITX2 upstream regulatory region as Green List (high evidence)
Eye Anterior Segment Abnormalities v1.22 PITX2 upstream regulatory region Sarah Milton Region: pitx2 upstream regulatory region has been classified as Green List (High Evidence).
Skeletal dysplasia v0.448 Sarah Milton Copied Region PITX1 upstream regulatory region from panel Mendeliome
Skeletal dysplasia v0.448 PITX1 upstream regulatory region Sarah Milton Region: PITX1 upstream regulatory region was added
Region: PITX1 upstream regulatory region was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: PITX1 upstream regulatory region.
Mode of inheritance for Region: PITX1 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: PITX1 upstream regulatory region were set to PMID: 30711920; 23022097; 25124102; 23587911
Phenotypes for Region: PITX1 upstream regulatory region were set to Liebenberg syndrome, MIM#186550
Hand and foot malformations v0.93 PITX1 upstream regulatory region Sarah Milton Classified Region: PITX1 upstream regulatory region as Green List (high evidence)
Hand and foot malformations v0.93 PITX1 upstream regulatory region Sarah Milton Region: pitx1 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4861 PITX1 upstream regulatory region Sarah Milton Classified Region: PITX1 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4861 PITX1 upstream regulatory region Sarah Milton Region: pitx1 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4860 PITX1 upstream regulatory region Sarah Milton Classified Region: PITX1 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4860 PITX1 upstream regulatory region Sarah Milton Region: pitx1 upstream regulatory region has been classified as Green List (High Evidence).
Regression v0.613 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Regression v0.613 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Regression v0.612 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Regression v0.612 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Ataxia v1.204 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Ataxia v1.204 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Leukodystrophy v0.395 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Leukodystrophy v0.395 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Mendeliome v1.4859 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Mendeliome v1.4859 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Craniosynostosis v1.86 IHH upstream regulatory region Sarah Milton Classified Region: IHH upstream regulatory region as Green List (high evidence)
Craniosynostosis v1.86 IHH upstream regulatory region Sarah Milton Region: ihh upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4858 IHH upstream regulatory region Sarah Milton Classified Region: IHH upstream regulatory region as Green List (high evidence)
Mendeliome v1.4858 IHH upstream regulatory region Sarah Milton Region: ihh upstream regulatory region has been classified as Green List (High Evidence).
Hand and foot malformations v0.92 IHH upstream regulatory region Sarah Milton Classified Region: IHH upstream regulatory region as Green List (high evidence)
Hand and foot malformations v0.92 IHH upstream regulatory region Sarah Milton Region: ihh upstream regulatory region has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.58 FOXF1 upstream regulatory region Sarah Milton Classified Region: FOXF1 upstream regulatory region as Green List (high evidence)
Pulmonary Arterial Hypertension v1.58 FOXF1 upstream regulatory region Sarah Milton Region: foxf1 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4857 FOXF1 upstream regulatory region Sarah Milton Classified Region: FOXF1 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4857 FOXF1 upstream regulatory region Sarah Milton Region: foxf1 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4856 FOXF1 upstream regulatory region Sarah Milton Classified Region: FOXF1 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4856 FOXF1 upstream regulatory region Sarah Milton Region: foxf1 upstream regulatory region has been classified as Green List (High Evidence).
Fetal anomalies v1.577 DLX5 downstream regulatory region Sarah Milton Classified Region: DLX5 downstream regulatory region as Green List (high evidence)
Fetal anomalies v1.577 DLX5 downstream regulatory region Sarah Milton Region: dlx5 downstream regulatory region has been classified as Green List (High Evidence).
Hand and foot malformations v0.91 DLX5 downstream regulatory region Sarah Milton Classified Region: DLX5 downstream regulatory region as Green List (high evidence)
Hand and foot malformations v0.91 DLX5 downstream regulatory region Sarah Milton Region: dlx5 downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4855 DLX5 downstream regulatory region Sarah Milton Classified Region: DLX5 downstream regulatory region as Green List (high evidence)
Mendeliome v1.4855 DLX5 downstream regulatory region Sarah Milton Region: dlx5 downstream regulatory region has been classified as Green List (High Evidence).
Facial papules v1.3 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Facial papules v1.3 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Basal Cell Cancer v1.3 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Basal Cell Cancer v1.3 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Facial papules v1.2 ARHGAP36 downstream regulatory region Sarah Milton Marked Region: ARHGAP36 downstream regulatory region as ready
Facial papules v1.2 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Red List (Low Evidence).
Hair disorders v0.90 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Hair disorders v0.90 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4854 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Mendeliome v1.4854 ARHGAP36 downstream regulatory region Sarah Milton Added comment: Comment on list classification: Discussed with ZS
Mendeliome v1.4854 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4853 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Mendeliome v1.4853 ARHGAP36 downstream regulatory region Sarah Milton Added comment: Comment on list classification: Discussed with ZS
Mendeliome v1.4853 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Facial papules v1.2 Sarah Milton Copied Region ARHGAP36 downstream regulatory region from panel Mendeliome
Facial papules v1.2 ARHGAP36 downstream regulatory region Sarah Milton Region: ARHGAP36 downstream regulatory region was added
Region: ARHGAP36 downstream regulatory region was added to Facial papules. Sources: Literature
regulatory region tags were added to Region: ARHGAP36 downstream regulatory region.
Mode of inheritance for Region: ARHGAP36 downstream regulatory region 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 Region: ARHGAP36 downstream regulatory region were set to PMID: 40015599; 35986704; 38713094
Phenotypes for Region: ARHGAP36 downstream regulatory region were set to Bazex-Dupre-Christol syndrome, MIM#301845
Basal Cell Cancer v1.2 Sarah Milton Copied Region ARHGAP36 downstream regulatory region from panel Mendeliome
Basal Cell Cancer v1.2 ARHGAP36 downstream regulatory region Sarah Milton Region: ARHGAP36 downstream regulatory region was added
Region: ARHGAP36 downstream regulatory region was added to Basal Cell Cancer. Sources: Literature
regulatory region tags were added to Region: ARHGAP36 downstream regulatory region.
Mode of inheritance for Region: ARHGAP36 downstream regulatory region 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 Region: ARHGAP36 downstream regulatory region were set to PMID: 40015599; 35986704; 38713094
Phenotypes for Region: ARHGAP36 downstream regulatory region were set to Bazex-Dupre-Christol syndrome, MIM#301845
Intellectual disability syndromic and non-syndromic v1.780 SUPT4H1 Freeman A reviewed gene: SUPT4H1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 41842694; Phenotypes: intellectual disability, motor disability, speech impairment, dystonia, craniofacial dysmorphism, skeletal anomalies, enamel hypoplasia.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.447 CCDC134 Zornitza Stark Marked gene: CCDC134 as ready
Skeletal dysplasia v0.447 CCDC134 Zornitza Stark Gene: ccdc134 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.447 Zornitza Stark Copied gene CCDC134 from panel Osteogenesis Imperfecta and Osteoporosis
Skeletal dysplasia v0.447 CCDC134 Zornitza Stark gene: CCDC134 was added
gene: CCDC134 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CCDC134 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC134 were set to 32181939; 34204301; 35019224
Phenotypes for gene: CCDC134 were set to Osteogenesis imperfecta, type XXII, MIM#619795
Skeletal dysplasia v0.446 C14orf80 Zornitza Stark Marked gene: C14orf80 as ready
Skeletal dysplasia v0.446 C14orf80 Zornitza Stark Gene: c14orf80 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.446 Zornitza Stark Copied gene C14orf80 from panel Mendeliome
Skeletal dysplasia v0.446 C14orf80 Zornitza Stark gene: C14orf80 was added
gene: C14orf80 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
new gene name tags were added to gene: C14orf80.
Mode of inheritance for gene: C14orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C14orf80 were set to 39979680; 38252227; 30842647
Phenotypes for gene: C14orf80 were set to Primary microcephaly, MONDO:0016660
Skeletal dysplasia v0.445 APC Zornitza Stark Marked gene: APC as ready
Skeletal dysplasia v0.445 APC Zornitza Stark Gene: apc has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.445 APC Zornitza Stark gene: APC was added
gene: APC was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: APC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APC were set to 30237576; 28383543; 25676610
Phenotypes for gene: APC were set to Syndromic disease, MONDO:0002254, APC-related
Review for gene: APC was set to RED
Added comment: PMID 25676610 reports 4 individuals from a Saudi consanguineous family with a homozygous APC splice‑site deletion and Cenani‑Lenz syndrome; PMID 28383543 reports another Saudi with homozygous APC splice‑site deletion and CLS; PMID 30237576 reports another Saudi individual with splice-site variant and CLS. All present with congenital limb malformations, syndactyly and scoliosis.

Likely founder variant. Possible multiple reports of same family.

All part of large cohorts with minimal additional information or functional validation, hence RED rating.
Sources: Literature
Congenital hypothyroidism v0.121 FOXA2 Chirag Patel Marked gene: FOXA2 as ready
Congenital hypothyroidism v0.121 FOXA2 Chirag Patel Gene: foxa2 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.121 Chirag Patel Copied gene FOXA2 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.121 FOXA2 Chirag Patel gene: FOXA2 was added
gene: FOXA2 was added to Congenital hypothyroidism. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: FOXA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXA2 were set to 28973288, 29329447, 30414530, 33729509, 31294511, 33999151
Phenotypes for gene: FOXA2 were set to Hypopituitarism, MONDO:0005152; Hyperinsulinism, MONDO:0002177
Pituitary hormone deficiency v0.227 TSHB Chirag Patel Marked gene: TSHB as ready
Pituitary hormone deficiency v0.227 TSHB Chirag Patel Gene: tshb has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.227 Chirag Patel Copied gene TSHB from panel Congenital hypothyroidism
Pituitary hormone deficiency v0.227 TSHB Chirag Patel gene: TSHB was added
gene: TSHB was added to Pituitary hormone deficiency. Sources: Expert Review Green,Genomics England PanelApp,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TSHB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSHB were set to 2792087; 27362444
Phenotypes for gene: TSHB were set to Congenital hypothyroidism; Hypothryoidism, congenital, nongoitrous 4, 275100; severe isolated central hypothyroidism
Callosome v0.595 FGF17 Zornitza Stark Marked gene: FGF17 as ready
Callosome v0.595 FGF17 Zornitza Stark Gene: fgf17 has been classified as Red List (Low Evidence).
Callosome v0.595 FGF17 Zornitza Stark Phenotypes for gene: FGF17 were changed from to Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270
Callosome v0.594 FGF17 Zornitza Stark Classified gene: FGF17 as Red List (low evidence)
Callosome v0.594 FGF17 Zornitza Stark Gene: fgf17 has been classified as Red List (Low Evidence).
Callosome v0.593 FGF17 Zornitza Stark reviewed gene: FGF17: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270; Mode of inheritance: None
Autoimmune Lymphoproliferative Syndrome v1.12 KRAS Zornitza Stark Tag somatic tag was added to gene: KRAS.
Hand and foot malformations v0.90 ISCA-37467-Gain Sarah Milton Source Expert list was removed from Region: ISCA-37467-Gain.
Source Expert list was removed from Region: ISCA-37467-Gain.
Source Literature was added to Region: ISCA-37467-Gain.
Tag regulatory region was added to Region: ISCA-37467-Gain.
Hair disorders v0.89 Sarah Milton Copied Region ARHGAP36 downstream regulatory region from panel Mendeliome
Hair disorders v0.89 ARHGAP36 downstream regulatory region Sarah Milton Region: ARHGAP36 downstream regulatory region was added
Region: ARHGAP36 downstream regulatory region was added to Hair disorders. Sources: Literature
regulatory region tags were added to Region: ARHGAP36 downstream regulatory region.
Mode of inheritance for Region: ARHGAP36 downstream regulatory region 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 Region: ARHGAP36 downstream regulatory region were set to PMID: 40015599; 35986704; 38713094
Phenotypes for Region: ARHGAP36 downstream regulatory region were set to Bazex-Dupre-Christol syndrome, MIM#301845
Mendeliome v1.4852 ARHGAP36 downstream regulatory region Sarah Milton Region: ARHGAP36 downstream regulatory region was added
Region: ARHGAP36 downstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: ARHGAP36 downstream regulatory region.
Mode of inheritance for Region: ARHGAP36 downstream regulatory region 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 Region: ARHGAP36 downstream regulatory region were set to PMID: 40015599; 35986704; 38713094
Phenotypes for Region: ARHGAP36 downstream regulatory region were set to Bazex-Dupre-Christol syndrome, MIM#301845
Review for Region: ARHGAP36 downstream regulatory region was set to GREEN
Added comment: ARHGAP36 is part of the Rho GTPase family and is a positive regulator of the SHH pathway.

At least 10 families have been reported in the literature with duplications in an agenic region downstream of ARHGAP36 presenting with Bazex-Dupre-Christol syndrome. This syndrome is characterised by a triad of follicular atrophoderma, hypotrichosis and basal cell neoplasms.

The duplications seen in affected individuals range from 18-135kb in size with the region thought to contain enhancers which increase expression of ARHGAP36.

Functional studies involving immunofluorescence of hair of affected individuals in telogen demonstrated increased expression of ARHGAP36.

Note: Coordinates used are the minimal region known to be duplicated in the reported cases.
Sources: Literature
Differences of Sex Development v1.55 ISCA-46303-Loss Sarah Milton Tag regulatory region was added to Region: ISCA-46303-Loss.
Skeletal dysplasia v0.444 DDX58 Zornitza Stark Marked gene: DDX58 as ready
Skeletal dysplasia v0.444 DDX58 Zornitza Stark Gene: ddx58 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.444 DDX58 Zornitza Stark changed review comment from: Comment when marking as ready: New HGNC approved name is RIGI.; to: New HGNC approved name is RIGI.

Syndrome with significant skeletal involvement.
Skeletal dysplasia v0.444 Zornitza Stark Copied gene DDX58 from panel Mendeliome
Skeletal dysplasia v0.444 DDX58 Zornitza Stark gene: DDX58 was added
gene: DDX58 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
new gene name tags were added to gene: DDX58.
Mode of inheritance for gene: DDX58 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX58 were set to 25620203; 30574673; 33495304
Phenotypes for gene: DDX58 were set to Singleton-Merten syndrome 2, MIM# 616298
Mode of pathogenicity for gene: DDX58 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Skeletal dysplasia v0.443 CWC27 Zornitza Stark Marked gene: CWC27 as ready
Skeletal dysplasia v0.443 CWC27 Zornitza Stark Gene: cwc27 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.443 CWC27 Zornitza Stark changed review comment from: Highly variable phenotype characterised by RP and brachydactyly. RP is slowly progressive, with night blindness occurring around 10 years of age (one individual reported with much more severe LCA phenotype). Additional features present in many individuals including frontal bossing, downslanting palpebral fissures, large columella, hypoplastic nares, micrognathia, and large low-set ears. Neurologic features included delays in speech, feeding, and walking, as well as intellectual disability (mild to moderate range). Congenital anomalies affecting heart/kidneys reported. Eight unrelated families reported.; to: Highly variable phenotype characterised by RP and metaphyseal chondrodysplasia, typically brachydactyly. RP is slowly progressive, with night blindness occurring around 10 years of age (one individual reported with much more severe LCA phenotype). Additional features present in many individuals including frontal bossing, downslanting palpebral fissures, large columella, hypoplastic nares, micrognathia, and large low-set ears. Neurologic features included delays in speech, feeding, and walking, as well as intellectual disability (mild to moderate range). Congenital anomalies affecting heart/kidneys reported. Eight unrelated families reported.
Skeletal dysplasia v0.443 Zornitza Stark Copied gene CWC27 from panel Mendeliome
Skeletal dysplasia v0.443 CWC27 Zornitza Stark gene: CWC27 was added
gene: CWC27 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CWC27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWC27 were set to 28285769; 31481716
Phenotypes for gene: CWC27 were set to Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410
Skeletal dysplasia v0.442 CSF1R Zornitza Stark Marked gene: CSF1R as ready
Skeletal dysplasia v0.442 CSF1R Zornitza Stark Gene: csf1r has been classified as Green List (High Evidence).
Skeletal dysplasia v0.442 Zornitza Stark Copied gene CSF1R from panel Brain Calcification
Skeletal dysplasia v0.442 CSF1R Zornitza Stark gene: CSF1R was added
gene: CSF1R was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: CSF1R was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSF1R were set to 30982609; 33749994; 34135456
Phenotypes for gene: CSF1R were set to Brain abnormalities, neurodegeneration, and dysosteosclerosis, MIM# 618476; BANDDOS
Skeletal dysplasia v0.441 CEP295 Zornitza Stark Classified gene: CEP295 as Green List (high evidence)
Skeletal dysplasia v0.441 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.440 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Skeletal dysplasia v0.440 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.440 CEP295 Zornitza Stark Classified gene: CEP295 as Green List (high evidence)
Skeletal dysplasia v0.440 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.439 CEP295 Zornitza Stark gene: CEP295 was added
gene: CEP295 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Skeletal dysplasia v0.438 CENPJ Zornitza Stark Marked gene: CENPJ as ready
Skeletal dysplasia v0.438 CENPJ Zornitza Stark Gene: cenpj has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.438 CENPJ Zornitza Stark Classified gene: CENPJ as Amber List (moderate evidence)
Skeletal dysplasia v0.438 CENPJ Zornitza Stark Gene: cenpj has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.437 CENPJ Zornitza Stark gene: CENPJ was added
gene: CENPJ was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CENPJ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPJ were set to 34068194
Phenotypes for gene: CENPJ were set to Seckel syndrome 4, MIM# 613676
Review for gene: CENPJ was set to AMBER
Added comment: PMID 34068194 reports 3 individuals from 2 unrelated families with autosomal recessive homozygous CENPJ variants presenting with Seckel syndrome. Functional assays (RT‑PCR splice assay, immunoblot, immunofluorescence) demonstrate aberrant splicing, reduced CENPJ protein and centrosome amplification, supporting pathogenicity.
Sources: Literature
Motor Neurone Disease v1.49 RBMX Zornitza Stark Marked gene: RBMX as ready
Motor Neurone Disease v1.49 RBMX Zornitza Stark Gene: rbmx has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v1.58 RBMX Zornitza Stark Marked gene: RBMX as ready
Early-onset Dementia v1.58 RBMX Zornitza Stark Gene: rbmx has been classified as Amber List (Moderate Evidence).
Growth failure v1.107 SLC6A17 Zornitza Stark Marked gene: SLC6A17 as ready
Growth failure v1.107 SLC6A17 Zornitza Stark Gene: slc6a17 has been classified as Green List (High Evidence).
Mendeliome v1.4851 SUPT6H Zornitza Stark Marked gene: SUPT6H as ready
Mendeliome v1.4851 SUPT6H Zornitza Stark Gene: supt6h has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.780 SUPT6H Zornitza Stark Marked gene: SUPT6H as ready
Intellectual disability syndromic and non-syndromic v1.780 SUPT6H Zornitza Stark Gene: supt6h has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.156 ADGB Zornitza Stark Marked gene: ADGB as ready
Infertility and Recurrent Pregnancy Loss v1.156 ADGB Zornitza Stark Gene: adgb has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.156 Zornitza Stark Copied gene ADGB from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.156 ADGB Zornitza Stark gene: ADGB was added
gene: ADGB was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ADGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGB were set to 38385883; 36995441
Phenotypes for gene: ADGB were set to Infertility disorder, MONDO:0005047, ADGB-related
Mendeliome v1.4851 ADGB Zornitza Stark Marked gene: ADGB as ready
Mendeliome v1.4851 ADGB Zornitza Stark Gene: adgb has been classified as Green List (High Evidence).
Mendeliome v1.4851 ADGB Zornitza Stark Classified gene: ADGB as Green List (high evidence)
Mendeliome v1.4851 ADGB Zornitza Stark Gene: adgb has been classified as Green List (High Evidence).
Speech apraxia v1.40 KDM5C Zornitza Stark Classified gene: KDM5C as Green List (high evidence)
Speech apraxia v1.40 KDM5C Zornitza Stark Gene: kdm5c has been classified as Green List (High Evidence).
Speech apraxia v1.39 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Speech apraxia v1.39 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Speech apraxia v1.39 SCN8A Zornitza Stark Classified gene: SCN8A as Green List (high evidence)
Speech apraxia v1.39 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Speech apraxia v1.38 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Speech apraxia v1.38 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Speech apraxia v1.38 PPP2R5D Zornitza Stark Classified gene: PPP2R5D as Green List (high evidence)
Speech apraxia v1.38 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Speech apraxia v1.37 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Speech apraxia v1.37 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Speech apraxia v1.37 FOXP1 Zornitza Stark Classified gene: FOXP1 as Green List (high evidence)
Speech apraxia v1.37 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Speech apraxia v1.36 SET Zornitza Stark Marked gene: SET as ready
Speech apraxia v1.36 SET Zornitza Stark Gene: set has been classified as Green List (High Evidence).
Speech apraxia v1.36 SET Zornitza Stark Classified gene: SET as Green List (high evidence)
Speech apraxia v1.36 SET Zornitza Stark Gene: set has been classified as Green List (High Evidence).
Speech apraxia v1.35 GNAI1 Zornitza Stark Marked gene: GNAI1 as ready
Speech apraxia v1.35 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Green List (High Evidence).
Speech apraxia v1.35 GNAI1 Zornitza Stark Classified gene: GNAI1 as Green List (high evidence)
Speech apraxia v1.35 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Green List (High Evidence).
Speech apraxia v1.34 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Speech apraxia v1.34 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Speech apraxia v1.34 SETD5 Zornitza Stark Classified gene: SETD5 as Green List (high evidence)
Speech apraxia v1.34 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Speech apraxia v1.33 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Speech apraxia v1.33 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Speech apraxia v1.33 SLC6A1 Zornitza Stark Classified gene: SLC6A1 as Green List (high evidence)
Speech apraxia v1.33 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Speech apraxia v1.32 SMARCA2 Zornitza Stark Marked gene: SMARCA2 as ready
Speech apraxia v1.32 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence).
Speech apraxia v1.32 SMARCA2 Zornitza Stark Classified gene: SMARCA2 as Green List (high evidence)
Speech apraxia v1.32 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence).
Mitochondrial disease v1.23 CHCHD4 Zornitza Stark Marked gene: CHCHD4 as ready
Mitochondrial disease v1.23 CHCHD4 Zornitza Stark Gene: chchd4 has been classified as Red List (Low Evidence).
Mitochondrial disease v1.23 Zornitza Stark Copied gene CHCHD4 from panel Mendeliome
Mitochondrial disease v1.23 CHCHD4 Zornitza Stark gene: CHCHD4 was added
gene: CHCHD4 was added to Mitochondrial disease. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CHCHD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHCHD4 were set to 41981912; 26004228
Phenotypes for gene: CHCHD4 were set to Mitochondrial disease, MONDO:0044970, CHCHD4-related
Mendeliome v1.4850 CHCHD4 Zornitza Stark Marked gene: CHCHD4 as ready
Mendeliome v1.4850 CHCHD4 Zornitza Stark Gene: chchd4 has been classified as Red List (Low Evidence).
Mendeliome v1.4850 CHCHD4 Zornitza Stark Phenotypes for gene: CHCHD4 were changed from IUGR; lactic acidosis; liver disease; hypoglycaemia; dystonia; hypertonia; regression to Mitochondrial disease, MONDO:0044970, CHCHD4-related
Mendeliome v1.4849 CHCHD4 Zornitza Stark Classified gene: CHCHD4 as Red List (low evidence)
Mendeliome v1.4849 CHCHD4 Zornitza Stark Gene: chchd4 has been classified as Red List (Low Evidence).
Mendeliome v1.4848 CHCHD4 Zornitza Stark reviewed gene: CHCHD4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease, MONDO:0044970, CHCHD4-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v1.107 CDK4 Lucy Spencer Classified gene: CDK4 as Green List (high evidence)
Growth failure v1.107 CDK4 Lucy Spencer Gene: cdk4 has been classified as Green List (High Evidence).
Growth failure v1.106 CDK4 Lucy Spencer Publications for gene: CDK4 were set to 40210435
Intellectual disability syndromic and non-syndromic v1.780 CDK4 Lucy Spencer Publications for gene: CDK4 were set to 40210435
Intellectual disability syndromic and non-syndromic v1.779 CDK4 Lucy Spencer Classified gene: CDK4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.779 CDK4 Lucy Spencer Gene: cdk4 has been classified as Green List (High Evidence).
Microcephaly v1.434 CDK4 Lucy Spencer Publications for gene: CDK4 were set to 40210435
Microcephaly v1.433 CDK4 Lucy Spencer Classified gene: CDK4 as Green List (high evidence)
Microcephaly v1.433 CDK4 Lucy Spencer Gene: cdk4 has been classified as Green List (High Evidence).
Microcephaly v1.432 Lucy Spencer Added reviews for gene CDK4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.778 Lucy Spencer Added reviews for gene CDK4 from panel Mendeliome
Growth failure v1.105 Lucy Spencer Added reviews for gene CDK4 from panel Mendeliome
Mendeliome v1.4848 CDK4 Lucy Spencer Publications for gene: CDK4 were set to 40210435
Mendeliome v1.4847 CDK4 Lucy Spencer reviewed gene: CDK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 41856556; Phenotypes: Microcephaly 31, primary, autosomal recessive, MIM# 621507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4847 ADGB Rylee Peters gene: ADGB was added
gene: ADGB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGB were set to 38385883; 36995441
Phenotypes for gene: ADGB were set to Infertility disorder, MONDO:0005047, ADGB-related
Review for gene: ADGB was set to GREEN
Added comment: PMID: 36995441 and PMID: 38385883 report four unrelated individuals with biallelic ADGB variants causing severe asthenoteratozoospermia. Functional studies including loss of ADGB protein in patient sperm and Adgb-/- male mice were infertile with immobile sperm.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.777 Lucy Spencer Copied gene SUPT6H from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.777 SUPT6H Lucy Spencer gene: SUPT6H was added
gene: SUPT6H was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SUPT6H was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUPT6H were set to 41864309
Phenotypes for gene: SUPT6H were set to Neurodevelopmental disorder, MONDO:0700092, SUPT6H-related
Mendeliome v1.4846 SUPT6H Lucy Spencer Classified gene: SUPT6H as Amber List (moderate evidence)
Mendeliome v1.4846 SUPT6H Lucy Spencer Gene: supt6h has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4845 SUPT6H Lucy Spencer gene: SUPT6H was added
gene: SUPT6H was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUPT6H was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUPT6H were set to 41864309
Phenotypes for gene: SUPT6H were set to Neurodevelopmental disorder, MONDO:0700092, SUPT6H-related
Review for gene: SUPT6H was set to AMBER
Added comment: PMID 41864309 reports 18 individuals from 18 unrelated families with heterozygous SUPT6H variants presenting with a neurodevelopmental disorder. All individuals were from large cohorts of individuals with developmental disorders (including the DECIPHER cohort) and phenotype information was limited but features included: autism‑spectrum, developmental delay, and occasional congenital heart disease or orofacial clefting.

All but 5 of the reported variants were present in gnomad with 3 or more hets. Asp175His, Lys256Arg, Arg380Gly, Gln517Lys and Trp1065* were all absent but 3 of these individuals were only listed as having CHD or autism. It is unclear whether the variants in this cohort were de novo however 4 of the 18 variants are in DECIPHER and all listed as de novo including Arg380Gly and Trp1065* which were absent from gnomad. Arg1495Gln and Arg1660Trp were also de novo in DECIPHER but have 6 and 34 hets respectively in gnomad.

Heterozygous KO mice were not viable and parvalbumin‑specific conditional Supt6 knockout mice recapitulate motor impairment, seizures and depression‑like behavior. No functional performed on the variants.

Only 5 of the 18 variants were absent from gnomad, limited phenotype information available and the things that are listed are not very consistent or specific, inheritance information not available for the vast majority. Amber but close to green
Sources: Literature
Mendeliome v1.4844 CHCHD4 Isabelle Adant gene: CHCHD4 was added
gene: CHCHD4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHCHD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHCHD4 were set to 41981912; 26004228
Phenotypes for gene: CHCHD4 were set to IUGR; lactic acidosis; liver disease; hypoglycaemia; dystonia; hypertonia; regression
Review for gene: CHCHD4 was set to RED
Added comment: 41981912
1 individual compound heterozygous for missense variant and large deletion
encompassing the whole CHCHD4 gene (and adjacent gene) of biparental inheritance,
presenting with IUGR, liver dysfunction, lactic acidosis and short-fasting
hypoglycaemia, developmental delay and regression, hypertonia and
dystonia. Early demise at 11months.
Minimal supporting biochemical evidence (protein expression studies) in patient-derived fibroblasts.

26004228 : Chchd4−/− mouse model
Biallelic Chchd4 in mouse embryos causes a developmental arrest coupled
with embryonic lethality at the onset of gastrulation. The developmental
retardation of Chchd4−/− embryos was accompanied by a major defect in the
expression of respiratory chain complex I subunit CI-20.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.776 WWP1 Zornitza Stark Marked gene: WWP1 as ready
Intellectual disability syndromic and non-syndromic v1.776 WWP1 Zornitza Stark Gene: wwp1 has been classified as Red List (Low Evidence).
Autism v0.250 WWP1 Zornitza Stark Marked gene: WWP1 as ready
Autism v0.250 WWP1 Zornitza Stark Gene: wwp1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.776 Zornitza Stark Copied gene WWP1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.776 WWP1 Zornitza Stark gene: WWP1 was added
gene: WWP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: WWP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WWP1 were set to 41786693; 32699206
Phenotypes for gene: WWP1 were set to Neurodevelopmental disorder, MONDO:0700092, WWP1-related
Autism v0.250 Zornitza Stark Copied gene WWP1 from panel Mendeliome
Autism v0.250 WWP1 Zornitza Stark gene: WWP1 was added
gene: WWP1 was added to Autism. Sources: Expert Review Red,Literature
Mode of inheritance for gene: WWP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WWP1 were set to 41786693; 32699206
Phenotypes for gene: WWP1 were set to Neurodevelopmental disorder, MONDO:0700092, WWP1-related
Mendeliome v1.4844 WWP1 Zornitza Stark Marked gene: WWP1 as ready
Mendeliome v1.4844 WWP1 Zornitza Stark Gene: wwp1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.414 PIGM Zornitza Stark Marked gene: PIGM as ready
Genetic Epilepsy v1.414 PIGM Zornitza Stark Gene: pigm has been classified as Green List (High Evidence).
Genetic Epilepsy v1.414 Zornitza Stark Copied gene PIGM from panel Mendeliome
Genetic Epilepsy v1.414 PIGM Zornitza Stark gene: PIGM was added
gene: PIGM was added to Genetic Epilepsy. Sources: Expert Review Green,Victorian Clinical Genetics Services
founder tags were added to gene: PIGM.
Mode of inheritance for gene: PIGM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGM were set to 31445883; 16767100; 41782195; 39912323; 39425582; 39119839
Phenotypes for gene: PIGM were set to Glycosylphosphatidylinositol deficiency, MIM# 610293; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Congenital Disorders of Glycosylation v1.88 PIGM Zornitza Stark Publications for gene: PIGM were set to 31445883; 16767100
Congenital Disorders of Glycosylation v1.87 PIGM Zornitza Stark Classified gene: PIGM as Green List (high evidence)
Congenital Disorders of Glycosylation v1.87 PIGM Zornitza Stark Gene: pigm has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.86 PIGM Zornitza Stark edited their review of gene: PIGM: Added comment: Sufficient evidence now for Green rating.; Changed rating: GREEN
Mendeliome v1.4844 PIGM Zornitza Stark Publications for gene: PIGM were set to 31445883; 16767100
Mendeliome v1.4843 PIGM Zornitza Stark Classified gene: PIGM as Green List (high evidence)
Mendeliome v1.4843 PIGM Zornitza Stark Gene: pigm has been classified as Green List (High Evidence).
Mendeliome v1.4843 PIGM Zornitza Stark Classified gene: PIGM as Green List (high evidence)
Mendeliome v1.4843 PIGM Zornitza Stark Gene: pigm has been classified as Green List (High Evidence).
Mendeliome v1.4842 PIGM Zornitza Stark reviewed gene: PIGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 41782195, 39912323, 39425582, 39119839, 31445883; Phenotypes: Glycosylphosphatidylinositol deficiency, MIM# 610293; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.576 Zornitza Stark removed gene:NME8 from the panel
Heterotaxy v1.45 NME8 Zornitza Stark Tag disputed tag was added to gene: NME8.
Ciliary Dyskinesia v1.77 NME8 Zornitza Stark Tag disputed tag was added to gene: NME8.
Cardiomyopathy_Paediatric v0.231 ASNA1 Zornitza Stark Tag new gene name tag was added to gene: ASNA1.
Fetal anomalies v1.575 EMG1 Zornitza Stark Publications for gene: EMG1 were set to 19463982
Fetal anomalies v1.574 EMG1 Zornitza Stark edited their review of gene: EMG1: Added comment: Affected individuals present with severe developmental delay, microcephaly, growth failure, micrognathia, joint contractures and early death. Functional studies show loss‑of‑function through protein destabilisation, reduced EMG1 levels, binucleate fibroblasts, G2/M arrest, impaired 18S rRNA processing and recapitulation of the phenotype in a mouse knock‑in model.

GDA to remain as AMBER as the same founder variant in the Hutterite population has been reported in the additional PMIDs and could potentially be the same families. Further reports would be required to upgrade to Green.; Changed publications: 19463982, 27798105, 26676230, 25708872
Intellectual disability syndromic and non-syndromic v1.775 EMG1 Zornitza Stark Publications for gene: EMG1 were set to 19463982
Intellectual disability syndromic and non-syndromic v1.774 EMG1 Zornitza Stark Tag founder tag was added to gene: EMG1.
Intellectual disability syndromic and non-syndromic v1.774 EMG1 Zornitza Stark edited their review of gene: EMG1: Added comment: Affected individuals present with severe developmental delay, microcephaly, growth failure, micrognathia, joint contractures and early death. Functional studies show loss‑of‑function through protein destabilisation, reduced EMG1 levels, binucleate fibroblasts, G2/M arrest, impaired 18S rRNA processing and recapitulation of the phenotype in a mouse knock‑in model.

GDA to remain as AMBER as the same founder variant in the Hutterite population has been reported in the additional PMIDs and could potentially be the same families. Further reports would be required to upgrade to Green.; Changed publications: 19463982, 27798105, 26676230, 25708872
Mendeliome v1.4842 EMG1 Zornitza Stark Tag founder tag was added to gene: EMG1.
Mendeliome v1.4842 EMG1 Zornitza Stark Publications for gene: EMG1 were set to 19463982
Mendeliome v1.4841 RASA2 Zornitza Stark Publications for gene: RASA2 were set to
Fetal anomalies v1.574 TOMM7 Zornitza Stark Marked gene: TOMM7 as ready
Fetal anomalies v1.574 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Fetal anomalies v1.574 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Fetal anomalies v1.573 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Fetal anomalies v1.573 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.259 TOMM7 Zornitza Stark Marked gene: TOMM7 as ready
Syndromic Retinopathy v0.259 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.259 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Syndromic Retinopathy v0.258 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Syndromic Retinopathy v0.258 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Mitochondrial disease v1.22 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Mitochondrial disease v1.21 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Mitochondrial disease v1.21 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Mitochondrial disease v1.20 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Changed rating: GREEN
Mitochondrial disease v1.20 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Added comment: TOMM7 encodes translocase of outer mitochondrial membrane 7 which is involved in transporting relevant proteins from the cytosol to the mitochondrial membrane.

PMIDs 36282599, 39615461 report 10 individuals from 8 unrelated families with a recurrent biallelic TOMM7 missense variant - p.(Pro29Leu).
The clinical presentation encompassed a progeroid syndrome with severe short stature (-4 to -7SD), mandibular hypoplasia, facial dysmorphism, atrophic macular scarring, microcephaly and moyamoya disease (5/10)

Functional studies in patient cells showed differing results based on cell type. Supportive knockout mouse and zebrafish studies. Mechanism of recurrent missense variant not fully elucidated.; Changed publications: 36299998, 36282599, 39615461
Microcephaly v1.431 TOMM7 Zornitza Stark Marked gene: TOMM7 as ready
Microcephaly v1.431 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Microcephaly v1.431 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Microcephaly v1.430 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Microcephaly v1.430 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Mendeliome v1.4840 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Mendeliome v1.4839 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Mendeliome v1.4839 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.155 TDRD6 Zornitza Stark Publications for gene: TDRD6 were set to 39764564; 39331689
Infertility and Recurrent Pregnancy Loss v1.154 TDRD6 Zornitza Stark Classified gene: TDRD6 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.154 TDRD6 Zornitza Stark Gene: tdrd6 has been classified as Green List (High Evidence).
Mendeliome v1.4838 TDRD6 Zornitza Stark Classified gene: TDRD6 as Green List (high evidence)
Mendeliome v1.4838 TDRD6 Zornitza Stark Gene: tdrd6 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.153 TDRD12 Zornitza Stark Publications for gene: TDRD12 were set to 40750267
Infertility and Recurrent Pregnancy Loss v1.152 TDRD12 Zornitza Stark Classified gene: TDRD12 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.152 TDRD12 Zornitza Stark Gene: tdrd12 has been classified as Green List (High Evidence).
Mendeliome v1.4837 TDRD12 Zornitza Stark Publications for gene: TDRD12 were set to 40750267
Mendeliome v1.4836 TDRD12 Zornitza Stark Classified gene: TDRD12 as Green List (high evidence)
Mendeliome v1.4836 TDRD12 Zornitza Stark Gene: tdrd12 has been classified as Green List (High Evidence).
Mitochondrial disease v1.20 OXA1L Zornitza Stark Publications for gene: OXA1L were set to 30201738
Mitochondrial disease v1.19 OXA1L Zornitza Stark Classified gene: OXA1L as Green List (high evidence)
Mitochondrial disease v1.19 OXA1L Zornitza Stark Gene: oxa1l has been classified as Green List (High Evidence).
Mitochondrial disease v1.18 OXA1L Zornitza Stark reviewed gene: OXA1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 40551575, 30201738; Phenotypes: Combined oxidative phosphorylation deficiency (MONDO:0000732), OXA1L-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v1.18 OXA1L Zornitza Stark Deleted their review
Mendeliome v1.4835 OXA1L Zornitza Stark Publications for gene: OXA1L were set to 30201738; 16435202
Mendeliome v1.4834 OXA1L Zornitza Stark Classified gene: OXA1L as Green List (high evidence)
Mendeliome v1.4834 OXA1L Zornitza Stark Gene: oxa1l has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.151 LRRC23 Zornitza Stark Marked gene: LRRC23 as ready
Infertility and Recurrent Pregnancy Loss v1.151 LRRC23 Zornitza Stark Gene: lrrc23 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.151 Zornitza Stark Copied gene LRRC23 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.151 LRRC23 Zornitza Stark gene: LRRC23 was added
gene: LRRC23 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: LRRC23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC23 were set to 37804054; 38091523; 39054792
Phenotypes for gene: LRRC23 were set to Spermatogenic failure 92, MIM# 620848
Mendeliome v1.4833 LRRC23 Zornitza Stark Publications for gene: LRRC23 were set to 37804054; 38091523
Mendeliome v1.4832 LRRC23 Zornitza Stark Classified gene: LRRC23 as Green List (high evidence)
Mendeliome v1.4832 LRRC23 Zornitza Stark Gene: lrrc23 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.774 KLHL15 Zornitza Stark Publications for gene: KLHL15 were set to 25644381; 24817631
Intellectual disability syndromic and non-syndromic v1.773 KLHL15 Zornitza Stark Classified gene: KLHL15 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.773 KLHL15 Zornitza Stark Gene: klhl15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.772 KLHL15 Zornitza Stark edited their review of gene: KLHL15: Added comment: Additional male individual presenting with impaired intelligence, short stature, frequent hypoglycaemia and periodic fever.
Hemizygous variant was identified in the proband c.736 C>T p.(Arg246*) - absent from gnomAD v4.1; Changed rating: GREEN; Changed publications: 25644381, 24817631, 37452054; Changed phenotypes: intellectual disability, X-linked 103 MONDO:0010508
Mendeliome v1.4831 KLHL15 Zornitza Stark Phenotypes for gene: KLHL15 were changed from Mental retardation, X-linked 103, MIM#300982 to intellectual disability, X-linked 103 MONDO:0010508
Mendeliome v1.4830 KLHL15 Zornitza Stark Publications for gene: KLHL15 were set to 25644381; 24817631
Mendeliome v1.4829 KLHL15 Zornitza Stark Classified gene: KLHL15 as Green List (high evidence)
Mendeliome v1.4829 KLHL15 Zornitza Stark Gene: klhl15 has been classified as Green List (High Evidence).
Fetal anomalies v1.572 HAND1 Zornitza Stark Publications for gene: HAND1 were set to 31286141; 29016838; 29317578; 29179274; 28112363; 27942761; 26581070
Fetal anomalies v1.571 HAND1 Zornitza Stark Classified gene: HAND1 as Green List (high evidence)
Fetal anomalies v1.571 HAND1 Zornitza Stark Gene: hand1 has been classified as Green List (High Evidence).
Fetal anomalies v1.570 HAND1 Zornitza Stark reviewed gene: HAND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39537763, 39107573, 38551686; Phenotypes: congenital heart disease, MONDO:0005453; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.540 HAND1 Zornitza Stark Publications for gene: HAND1 were set to 31286141; 29016838; 29317578; 29179274; 28112363; 27942761; 26581070
Congenital Heart Defect v0.539 HAND1 Zornitza Stark Classified gene: HAND1 as Green List (high evidence)
Congenital Heart Defect v0.539 HAND1 Zornitza Stark Gene: hand1 has been classified as Green List (High Evidence).
Mendeliome v1.4828 HAND1 Zornitza Stark Publications for gene: HAND1 were set to 31286141; 29016838; 29317578; 29179274; 28112363; 27942761; 26581070
Mendeliome v1.4827 HAND1 Zornitza Stark Classified gene: HAND1 as Green List (high evidence)
Mendeliome v1.4827 HAND1 Zornitza Stark Gene: hand1 has been classified as Green List (High Evidence).
Hair disorders v0.88 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to 31332722
Hair disorders v0.87 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Green List (high evidence)
Hair disorders v0.87 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.772 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to PMID: 28973399
Intellectual disability syndromic and non-syndromic v1.771 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.771 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.27 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to 26996949
Chromosome Breakage Disorders v1.26 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Green List (high evidence)
Chromosome Breakage Disorders v1.26 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.25 GTF2E2 Zornitza Stark edited their review of gene: GTF2E2: Added comment: 3 additional unrelated families presenting with brittle, tiger‑tail banded hair, ichthyosis, short stature, microcephaly, developmental delay, anemia, autism spectrum disorder and abnormal hemoglobin fractions reported with biallelic variants.; Changed rating: GREEN; Changed publications: 26996949, 37793898, 31064989, 28973399
Mendeliome v1.4826 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to 26996949
Mendeliome v1.4825 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Green List (high evidence)
Mendeliome v1.4825 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Green List (High Evidence).
Speech apraxia v1.31 SMARCA2 Hali Van Niel gene: SMARCA2 was added
gene: SMARCA2 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA2 were set to 41530369; 39931922; 32694869
Phenotypes for gene: SMARCA2 were set to Nicolaides-Baraitser syndrome (MIM#601358); Blepharophimosis-impaired intellectual development syndrome (MIM#619293)
Review for gene: SMARCA2 was set to GREEN
Added comment: Two reported individual with CAS and de novo missense variants (c.2870 A > G; p.(Gln957Arg); c.3484 C > T; p.(Arg1162Cys)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic findings from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with CAS and SMARCA2 variant (Supp Table 6).

Phenotype dependent on variant position along gene (PMID: 32694869). Both phenotypes implicated with CAS.
Sources: Expert List, Literature
Speech apraxia v1.31 SLC6A1 Hali Van Niel gene: SLC6A1 was added
gene: SLC6A1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SLC6A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC6A1 were set to 41530369; 39931922
Phenotypes for gene: SLC6A1 were set to Myoclonic-atonic epilepsy (MIM#616421
Review for gene: SLC6A1 was set to GREEN
Added comment: Reported individual with CAS and de novo missense variant (c.1097_1098delinsCT; p.(Leu366Pro)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline.

Mitchel et al. (2025; PMID: 39931922) report two individuals with dysarthria and SLC6A1 variant (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 SETD5 Hali Van Niel gene: SETD5 was added
gene: SETD5 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD5 were set to 41530369; 39931922
Phenotypes for gene: SETD5 were set to Intellectual developmental disorder, 23 (MIM#615761)
Review for gene: SETD5 was set to GREEN
Added comment: Reported individual with CAS and de novo splicing variant (c.2347-7 A > G) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report five individuals SETD5 variants (4 with CAS, 1 with dysarthria).

Unspecified speech delay/impairment reported commonly in individuals with SETD5 variants (PMID: 29484850)
Sources: Expert List, Literature
Speech apraxia v1.31 GNAI1 Hali Van Niel changed review comment from: Reported individual with CAS and de novo missense variant (c.518 A > T; p.(Asp173Val)) (Van Niel et al., 2026; PMID: 41530369), Validated C4 finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with dysarthria and GNAI1 variant (Supp Table 6).

Disorder characterised by impaired speech. Phenotype has variable expressivity ranging from mild to severe (PMID: 33473207); to: Reported individual with CAS and de novo missense variant (c.518 A > T; p.(Asp173Val)) (Van Niel et al., 2026; PMID: 41530369), Validated C4 finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with dysarthria and GNAI1 variant (Supp Table 6).

Disorder characterised by impaired speech. Phenotype is variable ranging from mild to severe (PMID: 33473207)
Speech apraxia v1.31 SET Hali Van Niel gene: SET was added
gene: SET was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SET were set to 41530369; 39931922
Phenotypes for gene: SET were set to Intellectual developmental disorder, 58 (MIM#618106).
Review for gene: SET was set to GREEN
Added comment: Reported individual with CAS and de novo nonsense variant (c.103_104del; p.(Ile35*)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with CAS and SET variant (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 FOXP1 Hali Van Niel changed review comment from: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature; to: Individual with CAS reported with nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369).

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 PPP2R5D Hali Van Niel changed review comment from: Individual with CAS reported with de novo nonsense variant, c.751 G > T; p.(Asp251Tyr) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with PPP2R5D variant with CAS (Supp Table 6).

Almost all individuals with a PPP2R5D variant have speech impairment, hallmark of disorder (PMID: 32074998)
Sources: Expert List, Literature; to: Individual with CAS reported with de novo missense variant, c.751 G > T; p.(Asp251Tyr) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with PPP2R5D variant with CAS (Supp Table 6).

Almost all individuals with a PPP2R5D variant have speech impairment, hallmark of disorder (PMID: 32074998)
Sources: Expert List, Literature
Mendeliome v1.4824 RASA2 Rylee Peters reviewed gene: RASA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 41854160, 25049390; Phenotypes: Noonan syndrome MONDO:0018997, RASA2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia and Chorea v0.346 GSX2 Zornitza Stark Publications for gene: GSX2 were set to 31412107
Dystonia and Chorea v0.345 GSX2 Zornitza Stark Classified gene: GSX2 as Green List (high evidence)
Dystonia and Chorea v0.345 GSX2 Zornitza Stark Gene: gsx2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.344 GSX2 Zornitza Stark edited their review of gene: GSX2: Added comment: Additional report of siblings from a consanguineous family affected with diencephalic-mesencephalic junction dysplasia
Proband was tested, and a homozygous variant was identified: c.747G>C (p.Trp249Cys) - variant is absent in gnomAD v4.1
The sibling was not tested but both healthy parents were identified as heterozygous.; Changed rating: GREEN; Changed publications: 31412107, 39119454; Changed phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 2 618646, Intellectual disability, Dystonia, Spastic tetra paresis
Intellectual disability syndromic and non-syndromic v1.770 GSX2 Zornitza Stark Publications for gene: GSX2 were set to 31412107
Intellectual disability syndromic and non-syndromic v1.769 GSX2 Zornitza Stark Classified gene: GSX2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.769 GSX2 Zornitza Stark Gene: gsx2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.768 GSX2 Zornitza Stark edited their review of gene: GSX2: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v1.768 GSX2 Zornitza Stark edited their review of gene: GSX2: Added comment: Additional report of siblings from a consanguineous family affected with diencephalic-mesencephalic junction dysplasia
Proband was tested, and a homozygous variant was identified: c.747G>C (p.Trp249Cys) - variant is absent in gnomAD v4.1
The sibling was not tested but both healthy parents were identified as heterozygous.; Changed publications: 31412107, 39119454; Changed phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 2 618646, Intellectual disability, Dystonia, Spastic tetra paresis
Cerebral Palsy v1.412 GSX2 Zornitza Stark Publications for gene: GSX2 were set to 31412107
Cerebral Palsy v1.411 GSX2 Zornitza Stark Classified gene: GSX2 as Green List (high evidence)
Cerebral Palsy v1.411 GSX2 Zornitza Stark Gene: gsx2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.410 GSX2 Zornitza Stark edited their review of gene: GSX2: Changed rating: GREEN
Cerebral Palsy v1.410 GSX2 Zornitza Stark edited their review of gene: GSX2: Added comment: PMID 39119454: Additional report of siblings from a consanguineous family affected with diencephalic-mesencephalic junction dysplasia Proband was tested, and a homozygous variant was identified: c.747G>C (p.Trp249Cys) - variant is absent in gnomAD v4.1 The sibling was not tested but both healthy parents were identified as heterozygous.; Changed publications: 31412107, 39119454; Changed phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 2 618646, Intellectual disability, Dystonia, Spastic tetra paresis
Mendeliome v1.4824 GSX2 Zornitza Stark Publications for gene: GSX2 were set to PMID: 31412107
Mendeliome v1.4823 GSX2 Zornitza Stark Classified gene: GSX2 as Green List (high evidence)
Mendeliome v1.4823 GSX2 Zornitza Stark Gene: gsx2 has been classified as Green List (High Evidence).
Speech apraxia v1.31 PPP2R5D Hali Van Niel gene: PPP2R5D was added
gene: PPP2R5D was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R5D were set to 41530369; 39931922; 32074998
Phenotypes for gene: PPP2R5D were set to Intellectual developmental disorder 35 (MIM#616355)
Review for gene: PPP2R5D was set to GREEN
Added comment: Individual with CAS reported with de novo nonsense variant, c.751 G > T; p.(Asp251Tyr) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with PPP2R5D variant with CAS (Supp Table 6).

Almost all individuals with a PPP2R5D variant have speech impairment, hallmark of disorder (PMID: 32074998)
Sources: Expert List, Literature
Bone Marrow Failure v1.145 RPL18 Zornitza Stark Publications for gene: RPL18 were set to PMID: 28280134, 32075953
Bone Marrow Failure v1.144 RPL18 Zornitza Stark reviewed gene: RPL18: Rating: AMBER; Mode of pathogenicity: None; Publications: 41851260, 40510848; Phenotypes: Diamond-Blackfan anemia 18, MONDO:0032668; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v1.57 RPL18 Zornitza Stark Phenotypes for gene: RPL18 were changed from Diamond-Blackfan anemia 18, MIM# 618310 to Diamond-Blackfan anaemia 18, MIM# 618310
Red cell disorders v1.56 RPL18 Zornitza Stark Publications for gene: RPL18 were set to 28280134; 32075953
Red cell disorders v1.55 RPL18 Zornitza Stark edited their review of gene: RPL18: Added comment: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

All variants are absent from gnomAD.; Changed publications: 28280134, 32075953, 40510848, 41851260; Changed phenotypes: Diamond-Blackfan anemia 18, MIM# 618310
Mendeliome v1.4822 RPL18 Zornitza Stark changed review comment from: Three recent studies add 3 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

PMID 28280134 reports one autosomal‑dominant family (father‑son) with heterozygous p.L51S; patient mononuclear cells display 36S pre‑rRNA accumulation, indicating a ribosome‑biogenesis defect.

All variants are absent from gnomAD.; to: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

All variants are absent from gnomAD.
Diamond Blackfan anaemia v1.22 RPL18 Zornitza Stark Phenotypes for gene: RPL18 were changed from Diamond-Blackfan anemia 18, MIM# 618310 to Diamond-Blackfan anaemia 18, MIM# 618310
Diamond Blackfan anaemia v1.21 RPL18 Zornitza Stark Publications for gene: RPL18 were set to 28280134; 32075953
Diamond Blackfan anaemia v1.20 RPL18 Zornitza Stark changed review comment from: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

Variants are absent from gnomAD.; to: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

Variants are absent from gnomAD.
Diamond Blackfan anaemia v1.20 RPL18 Zornitza Stark edited their review of gene: RPL18: Added comment: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

Variants are absent from gnomAD.; Changed publications: 28280134, 32075953, 41851260, 40510848; Changed phenotypes: Diamond-Blackfan anaemia 18, MIM# 618310
Speech apraxia v1.31 SCN8A Hali Van Niel gene: SCN8A was added
gene: SCN8A was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SCN8A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN8A were set to 41530369; 39931922
Phenotypes for gene: SCN8A were set to Cognitive impairment with or without cerebellar ataxia (MIM#614306)
Review for gene: SCN8A was set to GREEN
Added comment: One reported individual with CAS and de novo missense variant, c.417 G > A; p.(Met139Ile) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report two individuals with CAS and SCN8A variants (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 FOXP1 Hali Van Niel changed review comment from: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369)

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature; to: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 KDM5C Hali Van Niel reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 41530369, 39931922; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM#300534); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Speech apraxia v1.31 KDM5C Hali Van Niel Deleted their review
Speech apraxia v1.31 EHMT1 Hali Van Niel changed review comment from: Two reported individuals with CAS and EHMT1 variants (c.3229 C > T; p.(Gln1077*); c.2842 C > T; p.(Arg948Trp)) (Van Niel et al., 2026; PMID: 41530369)

Morrison et al. (2024; PMID: 38290825) reported 49 individuals with EHMT1 variants assessed by a speech pathologist, 34/49 with dysarthria and 29/49 with CAS.
Sources: Expert List; to: Two reported individuals with CAS and EHMT1 variants (c.3229 C > T; p.(Gln1077*); c.2842 C > T; p.(Arg948Trp)) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Morrison et al. (2024; PMID: 38290825) reported 49 individuals with EHMT1 variants assessed by a speech pathologist, 34/49 with dysarthria and 29/49 with CAS.
Sources: Expert List
Speech apraxia v1.31 EBF3 Hali Van Niel changed review comment from: Additional individuals:

One with dysarthria reported with de novo deletion in EBF3 (c.708_710delCAA; p.(Asn237del)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 4 individuals with EBF3 variants (1 with CAS, 3 with dysarthria); to: Additional individuals:

One with dysarthria reported with de novo deletion in EBF3 (c.708_710delCAA; p.(Asn237del)) (Van Niel et al., 2026; PMID: 41530369) Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report 4 individuals with EBF3 variants (1 with CAS, 3 with dysarthria)
Speech apraxia v1.31 CAMTA1 Hali Van Niel changed review comment from: One reported individual with CAS and dysarthria with a denovo frameshift variant (c.2072_2075del; p.(Thr691Argfs*35)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 3 individuals with CAMTA1 variants with dysarthria

Jacobs et al. (2020; PMID: 33131045) report 9 individuals with CAMTA1 variants, 5/9 with dysarthria and 9/9 with unspecified speech delay
Sources: Expert List, Literature; to: One reported individual with CAS and dysarthria with a denovo frameshift variant (c.2072_2075del; p.(Thr691Argfs*35)) (Van Niel et al., 2026; PMID: 41530369) Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report 3 individuals with CAMTA1 variants with dysarthria

Jacobs et al. (2020; PMID: 33131045) report 9 individuals with CAMTA1 variants, 5/9 with dysarthria and 9/9 with unspecified speech delay
Sources: Expert List, Literature
Speech apraxia v1.31 CACNA1A Hali Van Niel changed review comment from: Three reported individuals with CAS and LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature; to: Three reported individuals with CAS and LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic findings from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 GNAI1 Hali Van Niel reviewed gene: GNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 41530369, 9931922, 33473207); Phenotypes: Neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities (MIM#619854); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.4822 RPL18 Zornitza Stark edited their review of gene: RPL18: Changed rating: AMBER
Mendeliome v1.4822 RPL18 Zornitza Stark edited their review of gene: RPL18: Added comment: Three recent studies add 3 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

PMID 28280134 reports one autosomal‑dominant family (father‑son) with heterozygous p.L51S; patient mononuclear cells display 36S pre‑rRNA accumulation, indicating a ribosome‑biogenesis defect.

All variants are absent from gnomAD.; Changed rating: GREEN; Changed publications: 41851260, 40510848, 28280134; Changed phenotypes: Diamond-Blackfan anemia 18, MONDO:0032668
Speech apraxia v1.31 GNAI1 Hali Van Niel Deleted their review
Intellectual disability syndromic and non-syndromic v1.768 OLA1 Zornitza Stark Marked gene: OLA1 as ready
Intellectual disability syndromic and non-syndromic v1.768 OLA1 Zornitza Stark Gene: ola1 has been classified as Green List (High Evidence).
Microcephaly v1.429 OLA1 Zornitza Stark Marked gene: OLA1 as ready
Microcephaly v1.429 OLA1 Zornitza Stark Gene: ola1 has been classified as Green List (High Evidence).
Microcephaly v1.429 Zornitza Stark Copied gene OLA1 from panel Mendeliome
Microcephaly v1.429 OLA1 Zornitza Stark gene: OLA1 was added
gene: OLA1 was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: OLA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OLA1 were set to 41887223
Phenotypes for gene: OLA1 were set to Neurodevelopmental disorder, MONDO:0700092, OLA1-related
Intellectual disability syndromic and non-syndromic v1.768 Zornitza Stark Copied gene OLA1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.768 OLA1 Zornitza Stark gene: OLA1 was added
gene: OLA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: OLA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OLA1 were set to 41887223
Phenotypes for gene: OLA1 were set to Neurodevelopmental disorder, MONDO:0700092, OLA1-related
Mendeliome v1.4822 OLA1 Zornitza Stark Marked gene: OLA1 as ready
Mendeliome v1.4822 OLA1 Zornitza Stark Gene: ola1 has been classified as Green List (High Evidence).
Mendeliome v1.4822 OLA1 Zornitza Stark Phenotypes for gene: OLA1 were changed from Neurodevelopmental disorder with hypermobility to Neurodevelopmental disorder, MONDO:0700092, OLA1-related
Mendeliome v1.4821 OLA1 Zornitza Stark Classified gene: OLA1 as Green List (high evidence)
Mendeliome v1.4821 OLA1 Zornitza Stark Gene: ola1 has been classified as Green List (High Evidence).
Mendeliome v1.4820 OLA1 Zornitza Stark reviewed gene: OLA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, OLA1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hair disorders v0.86 KREMEN1 Zornitza Stark Publications for gene: KREMEN1 were set to 27049303; 27550540
Hair disorders v0.85 KREMEN1 Zornitza Stark Classified gene: KREMEN1 as Green List (high evidence)
Hair disorders v0.85 KREMEN1 Zornitza Stark Gene: kremen1 has been classified as Green List (High Evidence).
Hair disorders v0.84 KREMEN1 Zornitza Stark reviewed gene: KREMEN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28813618; Phenotypes: ectodermal dysplasia 13, hair/tooth type, MONDO:0044305; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ectodermal Dysplasia v0.112 KREMEN1 Zornitza Stark changed review comment from: Two additional unrelated families with suspected tooth agenesis reported in PMID 28813618.
Probands presented with mild clinical features of ectodermal dysplasia (parse hair, dry skin, sparse eyebrows and eyelashes, protruded lips, and heat intolerance)
Homozygous variants were identified in each proband (c.146C>G, p.T49R and c.773_778del - both rare in gnomAD v4.1 for AR gene); to: Two additional unrelated families with suspected tooth agenesis reported in PMID 28813618.
Probands presented with mild clinical features of ectodermal dysplasia (sparse hair, dry skin, sparse eyebrows and eyelashes, protruded lips, and heat intolerance)
Homozygous variants were identified in each proband (c.146C>G, p.T49R and c.773_778del - both rare in gnomAD v4.1 for AR gene)
Ectodermal Dysplasia v0.112 KREMEN1 Zornitza Stark Publications for gene: KREMEN1 were set to 29526031; 29526031
Ectodermal Dysplasia v0.111 KREMEN1 Zornitza Stark Classified gene: KREMEN1 as Green List (high evidence)
Ectodermal Dysplasia v0.111 KREMEN1 Zornitza Stark Gene: kremen1 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.110 KREMEN1 Zornitza Stark edited their review of gene: KREMEN1: Changed rating: GREEN
Ectodermal Dysplasia v0.110 KREMEN1 Zornitza Stark edited their review of gene: KREMEN1: Added comment: Two additional unrelated families with suspected tooth agenesis reported in PMID 28813618.
Probands presented with mild clinical features of ectodermal dysplasia (parse hair, dry skin, sparse eyebrows and eyelashes, protruded lips, and heat intolerance)
Homozygous variants were identified in each proband (c.146C>G, p.T49R and c.773_778del - both rare in gnomAD v4.1 for AR gene); Changed publications: 29526031, 29526031, 28813618
Mendeliome v1.4820 KREMEN1 Zornitza Stark Publications for gene: KREMEN1 were set to 27049303; 27550540
Mendeliome v1.4819 KREMEN1 Zornitza Stark Classified gene: KREMEN1 as Green List (high evidence)
Mendeliome v1.4819 KREMEN1 Zornitza Stark Gene: kremen1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.436 Zornitza Stark removed gene:SUPT4H1 from the panel
Intellectual disability syndromic and non-syndromic v1.767 NPRL2 Lucy Spencer Classified gene: NPRL2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.767 NPRL2 Lucy Spencer Gene: nprl2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.766 NPRL2 Lucy Spencer edited their review of gene: NPRL2: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v1.766 NPRL2 Lucy Spencer changed review comment from: Intellectual disability/developmental delay has been reported in some individuals with NPRL2-related epilepsy;

PMID: 30093711 3 patients with NPRL2 variants and 2 have ID, 2 also have brain abnormalities. NPRL2 forms the GATOR1 complex with DEPDC5 and NPLR3, the paper describes the phenotype of all 3 as overlapping- ID better reported in the other genes

PMID: 40804712 1 individual with mild ID and severe speech impairment. has a frameshift variant in NPRL2

PMID: 34376795 proband with seizures and dev delay/DEE, mother had ID and seizures. both had a canonical splice in NPRL2

PMID: 26505888 1 proband with ID and temporal lobe epilepsy. Had a maternally inherited missense Thr110Ser only 1 het i gnomad

Borderline amber/green for this panel
Sources: Literature; to: Intellectual disability/developmental delay has been reported in some individuals with NPRL2-related epilepsy;

PMID: 30093711 3 patients with NPRL2 variants and 2 have ID, 2 also have brain abnormalities. NPRL2 forms the GATOR1 complex with DEPDC5 and NPLR3, the paper describes the phenotype of all 3 as overlapping- ID better reported in the other genes

PMID: 40804712 1 individual with mild ID and severe speech impairment. has a frameshift variant in NPRL2

PMID: 34376795 proband with seizures and dev delay/DEE, mother had ID and seizures. both had a canonical splice in NPRL2

PMID: 26505888 1 proband with ID and temporal lobe epilepsy. Had a maternally inherited missense Thr110Ser only 1 het i gnomad

Sources: Literature
Mendeliome v1.4818 OLA1 Fahaz Nazer gene: OLA1 was added
gene: OLA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OLA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OLA1 were set to 41887223
Phenotypes for gene: OLA1 were set to Neurodevelopmental disorder with hypermobility
Review for gene: OLA1 was set to GREEN
Added comment: Autosomal recessive NDD with hypermobility

14 affected individuals from 9 unrelated families
6 individuals had significant microcephaly. All have ID.

Variant in Family 1: Arg143* - proven to cause complete loss of OLA1 protein on Western Blot.

Ola1 null mice are small for gestational age, exhibit developmental delay, and have high perinatal lethality

Functional evidence (C.Elegans model):
Assessed 2 independent LOF alleles.
Notable behavioral effects (reduced bending, and response to touch)
GABAergic motor neurons shows abnormal axonal architecture and projection defects
Sources: Literature
Skeletal dysplasia v0.435 Sarah Milton Copied gene SUPT4H1 from panel Mendeliome
Skeletal dysplasia v0.435 SUPT4H1 Sarah Milton gene: SUPT4H1 was added
gene: SUPT4H1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SUPT4H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT4H1 were set to 41842694
Phenotypes for gene: SUPT4H1 were set to Syndromic disease, MONDO:0002254, SUPT4H1-related
Intellectual disability syndromic and non-syndromic v1.766 Sarah Milton Copied gene SUPT4H1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.766 SUPT4H1 Sarah Milton gene: SUPT4H1 was added
gene: SUPT4H1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SUPT4H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT4H1 were set to 41842694
Phenotypes for gene: SUPT4H1 were set to Syndromic disease, MONDO:0002254, SUPT4H1-related
Amelogenesis imperfecta v1.15 Sarah Milton Copied gene SUPT4H1 from panel Mendeliome
Amelogenesis imperfecta v1.15 SUPT4H1 Sarah Milton gene: SUPT4H1 was added
gene: SUPT4H1 was added to Amelogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: SUPT4H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT4H1 were set to 41842694
Phenotypes for gene: SUPT4H1 were set to Syndromic disease, MONDO:0002254, SUPT4H1-related
Mendeliome v1.4818 SUPT4H1 Sarah Milton gene: SUPT4H1 was added
gene: SUPT4H1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUPT4H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT4H1 were set to 41842694
Phenotypes for gene: SUPT4H1 were set to Syndromic disease, MONDO:0002254, SUPT4H1-related
Review for gene: SUPT4H1 was set to GREEN
Added comment: SUPT4H1 encodes SPT4 which is a subunit of the DSIF complex that regulates RNA polymerase II transcription.

PMID 41842694 reports six individuals from three unrelated families with biallelic loss‑of‑function SUPT4H1 variants. 2 families were consanguineous, the other was not noted to have been.

Clinical presentations of affected individuals included moderate to severe intellectual disability, dystonia, speech impairment, dysmorphism, skeletal anomalies including vertebral fusion/bifid vertebrae and complete enamel hypoplasia in 6/6 individuals.
Variable additional features included epilepsy, spasticity and congenital heart defects.

Variants were homozygous with one extension and 2 missense variants. Loss of function presumed mechanism.

Supportive functional studies included altered transcriptomics and proteomics of other genes/proteins across patient samples. C. elegans knockout and variant knock‑in models demonstrated altered movement and behaviour.
Sources: Literature
Bleeding and Platelet Disorders v1.78 KLKB1 Zornitza Stark Classified gene: KLKB1 as Green List (high evidence)
Bleeding and Platelet Disorders v1.78 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Green List (High Evidence).
Mendeliome v1.4817 KLKB1 Zornitza Stark Publications for gene: KLKB1 were set to 15461630; 33073460
Mendeliome v1.4816 KLKB1 Zornitza Stark Classified gene: KLKB1 as Green List (high evidence)
Mendeliome v1.4816 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.765 LMAN2L Zornitza Stark Publications for gene: LMAN2L were set to PMID: 31020005; 26566883
Intellectual disability syndromic and non-syndromic v1.764 LMAN2L Zornitza Stark Classified gene: LMAN2L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.764 LMAN2L Zornitza Stark Gene: lman2l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.763 LMAN2L Zornitza Stark edited their review of gene: LMAN2L: Added comment: Upgrade AR GDA to Green given the reports of biallelic variants in affected individuals.
No new reports supportive of the AD GDA association.

PMID: 40221759 and 37667433 report two additional probands presenting with ID, global DD and other neurodevelopmental features. Both probands were compound heterozygous.; Changed rating: GREEN; Changed publications: 40221759, 37667433
Mendeliome v1.4815 LMAN2L Zornitza Stark Publications for gene: LMAN2L were set to 31020005; 26566883
Mendeliome v1.4814 LMAN2L Zornitza Stark Classified gene: LMAN2L as Green List (high evidence)
Mendeliome v1.4814 LMAN2L Zornitza Stark Gene: lman2l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.763 NPRL2 Zornitza Stark Marked gene: NPRL2 as ready
Intellectual disability syndromic and non-syndromic v1.763 NPRL2 Zornitza Stark Gene: nprl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4813 ATG12 Zornitza Stark Marked gene: ATG12 as ready
Mendeliome v1.4813 ATG12 Zornitza Stark Gene: atg12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.763 ATG12 Zornitza Stark Marked gene: ATG12 as ready
Intellectual disability syndromic and non-syndromic v1.763 ATG12 Zornitza Stark Gene: atg12 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v1.11 NSMCE3 Zornitza Stark Marked gene: NSMCE3 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v1.11 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.25 NSMCE3 Zornitza Stark Marked gene: NSMCE3 as ready
Chromosome Breakage Disorders v1.25 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.147 NSMCE3 Zornitza Stark Publications for gene: NSMCE3 were set to 27427983
Combined Immunodeficiency v1.146 NSMCE3 Zornitza Stark Classified gene: NSMCE3 as Green List (high evidence)
Combined Immunodeficiency v1.146 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.145 NSMCE3 Zornitza Stark edited their review of gene: NSMCE3: Changed rating: GREEN
Combined Immunodeficiency v1.145 NSMCE3 Zornitza Stark edited their review of gene: NSMCE3: Added comment: Total of five families with severe childhood‑onset lung disease, variable combined T‑cell/B‑cell immunodeficiency and chromosome breakage. Three of these families were homozygous for the same missense variant, p.(Leu264Phe) - articles below.

PMID: 40728043 | 1x paediatric case of lethal lung disease no history of failure to thrive, recurrent infections, or immunodeficiency. Compound heterozygous for p.(Lys260Ter) and p.(Pro105Ser).

PMID: 33741030 | five patients from two unrelated families with biallelic NSMCE3 missense variants did not reveal immunodeficiency; though all presented with severe lung disease. All five patients were homozygous for a single missense variant in NSMCE3, p.(Leu264Phe), that was previously identified in the initial report (PMID: 27427983).

PMID: 27427983 | 2x unrelated families with chromosome breakage syndrome with severe lung disease, 1xhom for p.(Leu264Phe), the other cHet for different missense.; Changed publications: 27427983, 40728043, 33741030
Pulmonary Fibrosis_Interstitial Lung Disease v1.11 Zornitza Stark Copied gene NSMCE3 from panel Mendeliome
Pulmonary Fibrosis_Interstitial Lung Disease v1.11 NSMCE3 Zornitza Stark gene: NSMCE3 was added
gene: NSMCE3 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NSMCE3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSMCE3 were set to 27427983; 40728043; 33741030
Phenotypes for gene: NSMCE3 were set to Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241
Chromosome Breakage Disorders v1.25 Zornitza Stark Copied gene NSMCE3 from panel Mendeliome
Chromosome Breakage Disorders v1.25 NSMCE3 Zornitza Stark gene: NSMCE3 was added
gene: NSMCE3 was added to Chromosome Breakage Disorders. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NSMCE3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSMCE3 were set to 27427983; 40728043; 33741030
Phenotypes for gene: NSMCE3 were set to Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241
Mendeliome v1.4813 NSMCE3 Zornitza Stark Publications for gene: NSMCE3 were set to 27427983
Mendeliome v1.4812 NSMCE3 Zornitza Stark Classified gene: NSMCE3 as Green List (high evidence)
Mendeliome v1.4812 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.763 Sangavi Sivagnanasundram Copied gene ATG12 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.763 ATG12 Sangavi Sivagnanasundram gene: ATG12 was added
gene: ATG12 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ATG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG12 were set to 41895291
Phenotypes for gene: ATG12 were set to ATG12-related neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4811 ATG12 Sangavi Sivagnanasundram edited their review of gene: ATG12: Changed phenotypes: ATG12-related neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4811 ATG12 Sangavi Sivagnanasundram Phenotypes for gene: ATG12 were changed from Neurodevelopmental disorder, MONDO:0700092 to ATG12-related neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4810 ATG12 Sangavi Sivagnanasundram Classified gene: ATG12 as Green List (high evidence)
Mendeliome v1.4810 ATG12 Sangavi Sivagnanasundram Gene: atg12 has been classified as Green List (High Evidence).
Mendeliome v1.4809 ATG12 Sangavi Sivagnanasundram gene: ATG12 was added
gene: ATG12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG12 were set to 41895291
Phenotypes for gene: ATG12 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: ATG12 was set to GREEN
Added comment: PMID 41895291 reports six individuals from five unrelated families with biallelic loss-of-function ATG12 variants causing a childhood‑onset neurodevelopmental disorder characterized by developmental delay, intellectual disability, congenital ataxia, hypotonia, seizures and cerebellar vermis hypoplasia. The paper reports on functional evidence supportive of pathogenicity.

Note: one of the reported variants (c.363+3A>T) had an FAF of 0.01706% in gnomAD and hasn't been reported in any other affected individuals.
Sources: Literature
Speech apraxia v1.31 FOXP1 Hali Van Niel gene: FOXP1 was added
gene: FOXP1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to (PMID: 41530369; 34109629; 39931922)
Phenotypes for gene: FOXP1 were set to intellectual disability-severe speech delay-mild dysmorphism syndrome (MONDO: 0013352)
Review for gene: FOXP1 was set to GREEN
Added comment: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369)

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 KDM5C Hali Van Niel reviewed gene: KDM5C: Rating: AMBER; Mode of pathogenicity: None; Publications: (PMID: 41530369, 39931922); Phenotypes: intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM#300534); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Speech apraxia v1.31 GNAI1 Hali Van Niel gene: GNAI1 was added
gene: GNAI1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: GNAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAI1 were set to PMID: 41530369; 39931922; 33473207
Phenotypes for gene: GNAI1 were set to neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities (MIM#619854)
Review for gene: GNAI1 was set to AMBER
Added comment: One reported individual with CAS and de novo missense variant (c.518 A > T; p.(Asp173Val)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report one individual with dysarthria and GNAI1 variant (Supp Table 6).

Disorder characterised by impaired speech. Phenotype has variable expressivity ranging from mild to severe (PMID: 33473207)
Sources: Expert List, Literature
Mendeliome v1.4808 MT-TQ Zornitza Stark Marked gene: MT-TQ as ready
Mendeliome v1.4808 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4808 MT-TQ Zornitza Stark Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700; 38730005; 32588991
Genetic Epilepsy v1.413 FOXJ3 Zornitza Stark Marked gene: FOXJ3 as ready
Genetic Epilepsy v1.413 FOXJ3 Zornitza Stark Gene: foxj3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.413 Zornitza Stark Copied gene FOXJ3 from panel Mendeliome
Genetic Epilepsy v1.413 FOXJ3 Zornitza Stark gene: FOXJ3 was added
gene: FOXJ3 was added to Genetic Epilepsy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: FOXJ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXJ3 were set to 41803108
Phenotypes for gene: FOXJ3 were set to Focal epilepsy, MONDO:0005384, FOXJ3-related
Mendeliome v1.4807 FOXJ3 Zornitza Stark Marked gene: FOXJ3 as ready
Mendeliome v1.4807 FOXJ3 Zornitza Stark Gene: foxj3 has been classified as Amber List (Moderate Evidence).
Common deletion and duplication syndromes v0.158 ISCA-46303-Loss Zornitza Stark Marked Region: ISCA-46303-Loss as ready
Common deletion and duplication syndromes v0.158 ISCA-46303-Loss Zornitza Stark Region: isca-46303-loss has been classified as Green List (High Evidence).
Clefting disorders v0.318 ISCA-46303-Loss Zornitza Stark Marked Region: ISCA-46303-Loss as ready
Clefting disorders v0.318 ISCA-46303-Loss Zornitza Stark Region: isca-46303-loss has been classified as Green List (High Evidence).
Congenital Heart Defect v0.538 FLNA Zornitza Stark Marked gene: FLNA as ready
Congenital Heart Defect v0.538 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Congenital Heart Defect v0.538 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to cardiac valvular dysplasia, X-linked MONDO:0010753
Congenital Heart Defect v0.537 FLNA Zornitza Stark Publications for gene: FLNA were set to
Congenital Heart Defect v0.536 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.570 RNU4-2 Zornitza Stark Marked gene: RNU4-2 as ready
Fetal anomalies v1.570 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Fetal anomalies v1.570 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from ReNU syndrome (MIM# 620851), AD to ReNU syndrome (MIM# 620851)
Fetal anomalies v1.569 RNU4-2 Zornitza Stark Classified gene: RNU4-2 as Green List (high evidence)
Fetal anomalies v1.569 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Speech apraxia v1.31 CAMTA1 Zornitza Stark Marked gene: CAMTA1 as ready
Speech apraxia v1.31 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Green List (High Evidence).
Speech apraxia v1.31 CAMTA1 Zornitza Stark Classified gene: CAMTA1 as Green List (high evidence)
Speech apraxia v1.31 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Green List (High Evidence).
Speech apraxia v1.30 EHMT1 Zornitza Stark Marked gene: EHMT1 as ready
Speech apraxia v1.30 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Green List (High Evidence).
Speech apraxia v1.30 EHMT1 Zornitza Stark Classified gene: EHMT1 as Green List (high evidence)
Speech apraxia v1.30 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Green List (High Evidence).
Speech apraxia v1.29 CACNA1A Hali Van Niel changed review comment from: Three reported individuals with CAS in LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature; to: Three reported individuals with CAS and LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature
Cardiomyopathy_Paediatric v0.231 Zornitza Stark removed gene:NDUFA5 from the panel
Intellectual disability syndromic and non-syndromic v1.762 Zornitza Stark removed gene:NDUFA5 from the panel
Speech apraxia v1.29 EHMT1 Hali Van Niel gene: EHMT1 was added
gene: EHMT1 was added to Speech apraxia. Sources: Expert List
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHMT1 were set to PMID: 41530369; PMID: 38290825
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome 1 (MIM#610253)
Review for gene: EHMT1 was set to GREEN
Added comment: Two reported individuals with CAS and EHMT1 variants (c.3229 C > T; p.(Gln1077*); c.2842 C > T; p.(Arg948Trp)) (Van Niel et al., 2026; PMID: 41530369)

Morrison et al. (2024; PMID: 38290825) reported 49 individuals with EHMT1 variants assessed by a speech pathologist, 34/49 with dysarthria and 29/49 with CAS.
Sources: Expert List
Mitochondrial disease v1.18 NDUFA5 Zornitza Stark Marked gene: NDUFA5 as ready
Mitochondrial disease v1.18 NDUFA5 Zornitza Stark Gene: ndufa5 has been classified as Green List (High Evidence).
Mitochondrial disease v1.18 NDUFA5 Zornitza Stark Phenotypes for gene: NDUFA5 were changed from Complex I deficiency to Mitochondrial disease, MONDO:0044970, NDUFA5-related
Mitochondrial disease v1.17 NDUFA5 Zornitza Stark reviewed gene: NDUFA5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease, MONDO:0044970, NDUFA5-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4807 NDUFA5 Zornitza Stark Marked gene: NDUFA5 as ready
Mendeliome v1.4807 NDUFA5 Zornitza Stark Gene: ndufa5 has been classified as Green List (High Evidence).
Mendeliome v1.4807 NDUFA5 Zornitza Stark Phenotypes for gene: NDUFA5 were changed from Complex I deficiency to Mitochondrial disease, MONDO:0044970, NDUFA5-related
Mendeliome v1.4806 NDUFA5 Zornitza Stark reviewed gene: NDUFA5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease, MONDO:0044970, NDUFA5-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.761 Zornitza Stark Copied gene NDUFA5 from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.761 NDUFA5 Zornitza Stark gene: NDUFA5 was added
gene: NDUFA5 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Complex I deficiency
Penetrance for gene: NDUFA5 were set to Complete
Cardiomyopathy_Paediatric v0.230 Zornitza Stark Copied gene NDUFA5 from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.230 NDUFA5 Zornitza Stark gene: NDUFA5 was added
gene: NDUFA5 was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Complex I deficiency
Penetrance for gene: NDUFA5 were set to Complete
Mendeliome v1.4806 Zornitza Stark Copied gene NDUFA5 from panel Mitochondrial disease
Mendeliome v1.4806 NDUFA5 Zornitza Stark gene: NDUFA5 was added
gene: NDUFA5 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Complex I deficiency
Penetrance for gene: NDUFA5 were set to Complete
Mitochondrial disease v1.17 NDUFA5 Zornitza Stark Classified gene: NDUFA5 as Green List (high evidence)
Mitochondrial disease v1.17 NDUFA5 Zornitza Stark Gene: ndufa5 has been classified as Green List (High Evidence).
Speech apraxia v1.29 EBF3 Hali Van Niel reviewed gene: EBF3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 41530369, PMID: 39931922; Phenotypes: hypotonia, ataxia, and delayed development syndrome (MIM#617330); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v1.29 CAMTA1 Hali Van Niel gene: CAMTA1 was added
gene: CAMTA1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMTA1 were set to PMID: 41530369; PMID: 39931922; PMID: 33131045
Phenotypes for gene: CAMTA1 were set to Cerebellar dysfunction with variable cognitive and behavioural abnormalities (MIM#614756)
Review for gene: CAMTA1 was set to GREEN
Added comment: One reported individual with CAS and dysarthria with a denovo frameshift variant (c.2072_2075del; p.(Thr691Argfs*35)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 3 individuals with CAMTA1 variants with dysarthria

Jacobs et al. (2020; PMID: 33131045) report 9 individuals with CAMTA1 variants, 5/9 with dysarthria and 9/9 with unspecified speech delay
Sources: Expert List, Literature
Skeletal Dysplasia_Fetal v0.250 Zornitza Stark Copied gene WDHD1 from panel Mendeliome
Skeletal Dysplasia_Fetal v0.250 WDHD1 Zornitza Stark gene: WDHD1 was added
gene: WDHD1 was added to Skeletal Dysplasia_Fetal. Sources: Expert Review Green,Literature
Mode of inheritance for gene: WDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDHD1 were set to 41962535
Phenotypes for gene: WDHD1 were set to microcephalic osteodysplastic primordial dwarfism, MONDO:0000060
Skeletal dysplasia v0.434 Zornitza Stark Copied gene WDHD1 from panel Mendeliome
Skeletal dysplasia v0.434 WDHD1 Zornitza Stark gene: WDHD1 was added
gene: WDHD1 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: WDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDHD1 were set to 41962535
Phenotypes for gene: WDHD1 were set to microcephalic osteodysplastic primordial dwarfism, MONDO:0000060
Fetal anomalies v1.568 Zornitza Stark Copied gene WDHD1 from panel Mendeliome
Fetal anomalies v1.568 WDHD1 Zornitza Stark gene: WDHD1 was added
gene: WDHD1 was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: WDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDHD1 were set to 41962535
Phenotypes for gene: WDHD1 were set to microcephalic osteodysplastic primordial dwarfism, MONDO:0000060
Mendeliome v1.4805 WDHD1 Zornitza Stark Marked gene: WDHD1 as ready
Mendeliome v1.4805 WDHD1 Zornitza Stark Gene: wdhd1 has been classified as Green List (High Evidence).
Mendeliome v1.4805 WDHD1 Zornitza Stark Classified gene: WDHD1 as Green List (high evidence)
Mendeliome v1.4805 WDHD1 Zornitza Stark Gene: wdhd1 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.41 Zornitza Stark Added reviews for gene CD3D from panel Severe Combined Immunodeficiency
Genomic newborn screening: ICoNS v0.40 Zornitza Stark Copied gene ARSB from panel Craniosynostosis
Genomic newborn screening: ICoNS v0.40 ARSB Zornitza Stark gene: ARSB was added
gene: ARSB was added to Genomic newborn screening: ICoNS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ARSB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARSB were set to Mucopolysaccharidosis VI (MPS6, MIM# 253200
Hypertrophic cardiomyopathy v1.26 POPDC2 Zornitza Stark Classified gene: POPDC2 as Green List (high evidence)
Hypertrophic cardiomyopathy v1.26 POPDC2 Zornitza Stark Gene: popdc2 has been classified as Green List (High Evidence).
Speech apraxia v1.29 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
Speech apraxia v1.29 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Speech apraxia v1.29 CACNA1A Zornitza Stark Classified gene: CACNA1A as Green List (high evidence)
Speech apraxia v1.29 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Speech apraxia v1.28 CACNA1A Hali Van Niel gene: CACNA1A was added
gene: CACNA1A was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to (PMID: 41530369); (PMID: 39931922)
Phenotypes for gene: CACNA1A were set to CACNA1A-related complex neurodevelopmental disorder (MONDO:0100254)
Review for gene: CACNA1A was set to GREEN
Added comment: Three reported individuals with CAS in LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature
Infertility and Recurrent Pregnancy Loss v1.150 CAPZA1 Zornitza Stark Marked gene: CAPZA1 as ready
Infertility and Recurrent Pregnancy Loss v1.150 CAPZA1 Zornitza Stark Gene: capza1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.150 Zornitza Stark Copied gene CAPZA1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.150 CAPZA1 Zornitza Stark gene: CAPZA1 was added
gene: CAPZA1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CAPZA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPZA1 were set to 41858859
Phenotypes for gene: CAPZA1 were set to Infertility disorder, MONDO:0005047
Mendeliome v1.4804 CAPZA1 Zornitza Stark Marked gene: CAPZA1 as ready
Mendeliome v1.4804 CAPZA1 Zornitza Stark Gene: capza1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4804 CAPZA1 Zornitza Stark Classified gene: CAPZA1 as Amber List (moderate evidence)
Mendeliome v1.4804 CAPZA1 Zornitza Stark Gene: capza1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4803 CAPZA1 Zornitza Stark gene: CAPZA1 was added
gene: CAPZA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPZA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPZA1 were set to 41858859
Phenotypes for gene: CAPZA1 were set to Infertility disorder, MONDO:0005047
Review for gene: CAPZA1 was set to AMBER
Added comment: PMID 41858859 reports four individuals from different families with autosomal recessive asthenozoospermia due to a homozygous missense variant c.11T>C (p.Phe4Ser) in CAPZA1. Segregation analysis confirms biallelic inheritance, and mouse knockout and in‑vitro assays demonstrate reduced CAPZA1 protein and disrupted sperm flagellar structure, providing supportive functional evidence.
Sources: Literature
Brain Calcification v2.9 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Brain Calcification v2.8 XPR1 Zornitza Stark edited their review of gene: XPR1: Added comment: PMID 41834789 reports 13 affected individuals from 4 consanguineous families with a homozygous loss‑of‑function missense variant (c.1811G>A; p.Arg604Gln) causing neonatal‑onset severe multisystem disease (brain calcifications, developmental delay, hypophosphataemia, cardiopulmonary involvement). Likely founder variant. Remains to be seen whether the biallelic disease relates specifically to this variant. Amber for this association -- caution with other variants warranted.; Changed publications: 25938945, 41834789; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4802 XPR1 Zornitza Stark Publications for gene: XPR1 were set to 25938945
Mendeliome v1.4801 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4800 XPR1 Zornitza Stark edited their review of gene: XPR1: Added comment: PMID 41834789 reports 13 affected individuals from 4 consanguineous families with a homozygous loss‑of‑function missense variant (c.1811G>A; p.Arg604Gln) causing neonatal‑onset severe multisystem disease (brain calcifications, developmental delay, hypophosphataemia, cardiopulmonary involvement).

Likely founder variant. Remains to be seen whether the biallelic disease relates specifically to this variant. Amber for this association -- caution with other variants warranted.; Changed publications: 41834789; Changed phenotypes: Basal ganglia calcification, idiopathic, 6, MONDO:0014628; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v1.54 Sarah Milton Copied Region SOX9 upstream regulatory region gain from panel Mendeliome
Differences of Sex Development v1.54 SOX9 upstream regulatory region gain Sarah Milton Region: SOX9 upstream regulatory region gain was added
Region: SOX9 upstream regulatory region gain was added to Differences of Sex Development. Sources: Literature
regulatory region tags were added to Region: SOX9 upstream regulatory region gain.
Mode of inheritance for Region: SOX9 upstream regulatory region gain was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: SOX9 upstream regulatory region gain were set to PMID: 37551848; 30552336; 31661700
Phenotypes for Region: SOX9 upstream regulatory region gain were set to 46XX sex reversal 2, MIM#278850
Penetrance for Region: SOX9 upstream regulatory region gain were set to Incomplete
Mendeliome v1.4800 SOX9 upstream regulatory region gain Sarah Milton changed review comment from: The upstream regulatory region of SOX9 has been demonstrated to have key roles in transcription factor binding including binding of SRY.

Increased dosage of this agenic region has been demonstrated in a number of individuals to result in 46XX sex reversal with a varying phenotype from DSD to phenotypic male.

The coordinates used in this entry are the minimal critical region however reported duplications range from 3.7kb to 780kb.
Incomplete penetrance has been observed.

Supportive functional studies in the form of mouse models and luciferase reporter assays have been published.

Note: Duplications of this region in 46,XY individuals don't result in a phenotype. Refer to ISCA-46303 loss entry.
Sources: Literature; to: The upstream regulatory region of SOX9 has been demonstrated to have key roles in transcription factor binding including binding of SRY.

Increased dosage of this agenic region has been demonstrated in a number of individuals to result in 46XX sex reversal with a varying phenotype from DSD to phenotypic male.

The coordinates used in this entry are the minimal critical region affecting XYSR enhancer however reported duplications range from 3.7kb to 780kb.
Incomplete penetrance has been observed.

Supportive functional studies in the form of mouse models and luciferase reporter assays have been published.

Note: Duplications of this region in 46,XY individuals don't result in a phenotype. Refer to ISCA-46303 loss entry.
Sources: Literature
Mendeliome v1.4800 SOX9 upstream regulatory region gain Sarah Milton Region: SOX9 upstream regulatory region gain was added
Region: SOX9 upstream regulatory region gain was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: SOX9 upstream regulatory region gain.
Mode of inheritance for Region: SOX9 upstream regulatory region gain was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: SOX9 upstream regulatory region gain were set to PMID: 37551848; 30552336; 31661700
Phenotypes for Region: SOX9 upstream regulatory region gain were set to 46XX sex reversal 2, MIM#278850
Penetrance for Region: SOX9 upstream regulatory region gain were set to Incomplete
Review for Region: SOX9 upstream regulatory region gain was set to GREEN
Added comment: The upstream regulatory region of SOX9 has been demonstrated to have key roles in transcription factor binding including binding of SRY.

Increased dosage of this agenic region has been demonstrated in a number of individuals to result in 46XX sex reversal with a varying phenotype from DSD to phenotypic male.

The coordinates used in this entry are the minimal critical region however reported duplications range from 3.7kb to 780kb.
Incomplete penetrance has been observed.

Supportive functional studies in the form of mouse models and luciferase reporter assays have been published.

Note: Duplications of this region in 46,XY individuals don't result in a phenotype. Refer to ISCA-46303 loss entry.
Sources: Literature
Congenital Heart Defect v0.535 FLNA Sangavi Sivagnanasundram reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29334594, 20301392; Phenotypes: cardiac valvular dysplasia, X-linked MONDO:0010753; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v1.53 ISCA-46303-Loss Sarah Milton Publications for Region: ISCA-46303-Loss were changed from PMID: 24934569, 26663529, 19234473, 26152199, 30552336 to PMID: 41272840, 24934569, 26663529, 19234473, 26152199, 30552336
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.

Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 have been associated with Pierre Robin syndrome, campomelic dysplasia, acampomelic dysplasia as well as 46,XY sex reversal.

This region has been curated by Clingen for the Pierre Robin syndrome phenotype and has been called HI3. Coordinates were based on the largest region found in affected individuals.

There are a number of enhancer elements within this region of which there are proposed to be four clusters: a proximal cluster between 50-375 kb, a sex-determining interval RevSex region between 517-595 kb, a distal cluster between 601 and 932 kb, and a PRS cluster between 1.03–1.26 Mb. Defining genotype phenotype has not been conclusively established within the literature in this region however there are some noted correlations.

Incomplete penetrance has been noted for the 46,XY sex reversal with approx 75% of individuals with deletions in this region demonstrating a DSD phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.
Sources: ClinGen
Clefting disorders v0.318 ISCA-46303-Loss Sarah Milton Phenotypes for Region: ISCA-46303-Loss were changed from to Pierre Robin syndrome MIM#261800
Tag regulatory region was added to Region: ISCA-46303-Loss.
Clefting disorders v0.317 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 have been associated with Pierre Robin syndrome, campomelic dysplasia, acampomelic dysplasia as well as 46,XY sex reversal.

This region has been curated by Clingen for the Pierre Robin syndrome phenotype and has been called HI3. Coordinates were based on the largest region found in affected individuals.

There are a number of enhancer elements within this region of which there are proposed to be four clusters: a proximal cluster between 50-375 kb, a sex-determining interval RevSex region between 517-595 kb, a distal cluster between 601 and 932 kb, and a PRS cluster between 1.03–1.26 Mb. Defining genotype phenotype has not been conclusively established within the literature in this region however there are some noted correlations.

Incomplete penetrance has been noted for the 46,XY sex reversal with approx 75% of individuals with deletions in this region demonstrating a DSD phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.

Sources: ClinGen
Common deletion and duplication syndromes v0.158 ISCA-46303-Loss Sarah Milton Phenotypes for Region: ISCA-46303-Loss were changed from to Campomelic dysplasia MIM#114290, Acampomelic campomelic dysplasia MIM#114290, 46XY sex reversal 10 MIM#616425, Pierre Robin syndrome MIM#261800
Publications for Region: ISCA-46303-Loss were changed from PMID: 24934569, 26663529, 19234473, 26152199, 30552336 to PMID: 41272840. 24934569, 26663529, 19234473, 26152199, 30552336
Tag regulatory region was added to Region: ISCA-46303-Loss.
Common deletion and duplication syndromes v0.157 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 have been associated with Pierre Robin syndrome, campomelic dysplasia, acampomelic dysplasia as well as 46,XY sex reversal.

This region has been curated by Clingen for the Pierre Robin syndrome phenotype and has been called HI3. Coordinates were based on the largest region found in affected individuals.

There are a number of enhancer elements within this region of which there are proposed to be four clusters: a proximal cluster between 50-375 kb, a sex-determining interval RevSex region between 517-595 kb, a distal cluster between 601 and 932 kb, and a PRS cluster between 1.03–1.26 Mb. Defining genotype phenotype has not been conclusively established within the literature in this region however there are some noted correlations.

Incomplete penetrance has been noted for the 46,XY sex reversal with approx 75% of individuals with deletions in this region demonstrating a DSD phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.

Sources: ClinGen
Common deletion and duplication syndromes v0.157 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.
Sources: ClinGen
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.

Sources: ClinGen
Common deletion and duplication syndromes v0.157 ISCA-46303-Loss Sarah Milton Classified Region: ISCA-46303-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.157 ISCA-46303-Loss Sarah Milton Region: isca-46303-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.156 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen
Clefting disorders v0.317 ISCA-46303-Loss Sarah Milton Classified Region: ISCA-46303-Loss as Green List (high evidence)
Clefting disorders v0.317 ISCA-46303-Loss Sarah Milton Region: isca-46303-loss has been classified as Green List (High Evidence).
Clefting disorders v0.316 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia..
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia..
Sources: ClinGen
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen
Clefting disorders v0.316 TBX15 Zornitza Stark Marked gene: TBX15 as ready
Clefting disorders v0.316 TBX15 Zornitza Stark Gene: tbx15 has been classified as Green List (High Evidence).
Clefting disorders v0.316 TBX15 Zornitza Stark Phenotypes for gene: TBX15 were changed from COUSIN SYNDROME to Pelviscapular dysplasia (Cousin syndrome), MONDO:0009845; Cleft palate, MONDO:0016064, TBX15-related
Clefting disorders v0.315 TBX15 Zornitza Stark Publications for gene: TBX15 were set to
Clefting disorders v0.314 TBX15 Zornitza Stark Mode of inheritance for gene: TBX15 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting disorders v0.313 TBX15 Zornitza Stark Classified gene: TBX15 as Green List (high evidence)
Clefting disorders v0.313 TBX15 Zornitza Stark Gene: tbx15 has been classified as Green List (High Evidence).
Clefting disorders v0.312 TBX15 Zornitza Stark reviewed gene: TBX15: Rating: GREEN; Mode of pathogenicity: None; Publications: 19068278, 24039145, 41904889, 40693652, 36124393; Phenotypes: Pelviscapular dysplasia (Cousin syndrome), MONDO:0009845, Cleft palate, MONDO:0016064, TBX15-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4799 TBX15 Zornitza Stark Phenotypes for gene: TBX15 were changed from Cousin syndrome, MIM# 260660 to Cousin syndrome, MIM# 260660; Cleft palate, MONDO:0016064, TBX15-related
Mendeliome v1.4798 TBX15 Zornitza Stark Publications for gene: TBX15 were set to 19068278; 24039145
Mendeliome v1.4797 TBX15 Zornitza Stark Mode of inheritance for gene: TBX15 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4796 TBX15 Zornitza Stark edited their review of gene: TBX15: Changed publications: 41904889, 40693652, 36124393, 40693652
Mendeliome v1.4796 TBX15 Zornitza Stark changed review comment from: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.

Evidence for mono allelic is Amber, given borderline number of families and postulated association with a relatively common phenotype, which is typically not monogenic.; to: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.

Evidence for mono allelic is Amber, given borderline number of families and postulated association with a relatively common phenotype, which is typically not monogenic.

PMID 40693652 reports a further individual with biallelic TBX15 missense (c.709A>G) causing a milder form of Cousin syndrome.
Mendeliome v1.4796 TBX15 Zornitza Stark changed review comment from: Cleft palate, multiple skeletal abnormalities. Three families reported.; to: Cousin syndrome: Cleft palate, multiple skeletal abnormalities. Three families reported.
Mendeliome v1.4796 TBX15 Zornitza Stark changed review comment from: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.; to: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.

Evidence for mono allelic is Amber, given borderline number of families and postulated association with a relatively common phenotype, which is typically not monogenic.
Mendeliome v1.4796 TBX15 Zornitza Stark edited their review of gene: TBX15: Added comment: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.; Changed publications: 41904889, 40693652, 36124393; Changed phenotypes: Pelviscapular dysplasia (Cousin syndrome), MONDO:0009845, Cleft palate, MONDO:0016064, TBX15-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.760 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to
Intellectual disability syndromic and non-syndromic v1.759 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.758 SLC20A2 Zornitza Stark Classified gene: SLC20A2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.758 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.757 SLC20A2 Zornitza Stark changed review comment from: Progressive neurological condition, ID is not part of the phenotype.; to: Mono-allelic association: Progressive neurological condition, ID is not part of the phenotype.
Intellectual disability syndromic and non-syndromic v1.757 SLC20A2 Zornitza Stark edited their review of gene: SLC20A2: Added comment: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

Gene is classically associated with a milder mono-allelic disorder, which typically does not involve ID.; Changed rating: AMBER; Changed publications: 41458256, 35881308; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v2.8 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to 22327515; 23334463
Brain Calcification v2.7 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Brain Calcification v2.6 SLC20A2 Zornitza Stark changed review comment from: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

PMID 34267336 reports a consanguineous family including a 55‑year‑old woman homozygous for the missense variant c.211C>T (p.Arg71Cys) who had extensive basal ganglia calcifications, psychiatric manifestations and progressive Parkinsonism.; to: Bi-allelic association:

PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

PMID 34267336 reports a consanguineous family including a 55‑year‑old woman homozygous for the missense variant c.211C>T (p.Arg71Cys) who had extensive basal ganglia calcifications, psychiatric manifestations and progressive Parkinsonism.
Brain Calcification v2.6 SLC20A2 Zornitza Stark changed review comment from: Over 50 families reported. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache.; to: Mono-allelic association: Over 50 families reported. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache.
Brain Calcification v2.6 SLC20A2 Zornitza Stark edited their review of gene: SLC20A2: Added comment: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

PMID 34267336 reports a consanguineous family including a 55‑year‑old woman homozygous for the missense variant c.211C>T (p.Arg71Cys) who had extensive basal ganglia calcifications, psychiatric manifestations and progressive Parkinsonism.; Changed publications: 22327515, 23334463, 24209445, 23437308, 32705272, 27943094; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v1.412 SLC20A2 Zornitza Stark Marked gene: SLC20A2 as ready
Genetic Epilepsy v1.412 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.412 SLC20A2 Zornitza Stark Classified gene: SLC20A2 as Amber List (moderate evidence)
Genetic Epilepsy v1.412 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.411 SLC20A2 Zornitza Stark gene: SLC20A2 was added
gene: SLC20A2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLC20A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC20A2 were set to 41458256; 35881308
Phenotypes for gene: SLC20A2 were set to Basal ganglia calcification, idiopathic, 1, MIM# 213600
Review for gene: SLC20A2 was set to AMBER
Added comment: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

Gene is classically associated with a milder mono-allelic disorder, which typically does not involve seizures.
Sources: Literature
Mendeliome v1.4796 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to 22327515; 23334463; 24209445; 23437308; 32705272; 27943094
Mendeliome v1.4795 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4794 SLC20A2 Zornitza Stark edited their review of gene: SLC20A2: Added comment: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

PMID 34267336 reports a consanguineous family including a 55‑year‑old woman homozygous for the missense variant c.211C>T (p.Arg71Cys) who had extensive basal ganglia calcifications, psychiatric manifestations and progressive Parkinsonism.; Changed publications: 22327515, 23334463, 41458256, 35881308, 34267336; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.149 PADI6 Zornitza Stark changed review comment from: Inheritance is biallelic: PMID 34987164 reports 13 unrelated families (14 patients) with biallelic loss‑of‑function PADI6 variants causing early embryonic arrest (2‑7 cell stage) and female infertility.; to: PMID 34987164 reports 13 unrelated families (14 patients) with biallelic loss‑of‑function PADI6 variants causing early embryonic arrest (2‑7 cell stage) and female infertility.
Infertility and Recurrent Pregnancy Loss v1.149 PADI6 Zornitza Stark Publications for gene: PADI6 were set to 29693651; 33583041; 33221824; 27730629; 27545678
Infertility and Recurrent Pregnancy Loss v1.148 PADI6 Zornitza Stark reviewed gene: PADI6: Rating: GREEN; Mode of pathogenicity: None; Publications: 34987164; Phenotypes: Oocyte/zygote/embryo maturation arrest 16, #MIM 617234; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v1.11 PADI6 Zornitza Stark Publications for gene: PADI6 were set to 27545678; 33221824; 32928291
Imprinting disorders v1.10 PADI6 Zornitza Stark Mode of inheritance for gene: PADI6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v1.9 PADI6 Zornitza Stark reviewed gene: PADI6: Rating: GREEN; Mode of pathogenicity: None; Publications: 34987164, 35296332; Phenotypes: Pre-implantation embryonic lethality 2 MIM#617234, Multi locus imprinting disturbance in offspring; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4794 PADI6 Zornitza Stark Publications for gene: PADI6 were set to 29693651; 33583041; 32928291; 33221824; 27545678
Mendeliome v1.4793 PADI6 Zornitza Stark Mode of inheritance for gene: PADI6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4792 PADI6 Zornitza Stark reviewed gene: PADI6: Rating: GREEN; Mode of pathogenicity: None; Publications: 34987164, 35296332; Phenotypes: Pre-implantation embryonic lethality 2 MIM#617234, Multi locus imprinting disturbance in offspring; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4792 KDM1A Zornitza Stark Phenotypes for gene: KDM1A were changed from Cleft palate, psychomotor retardation, and distinctive facial features 616728; Multiple myeloma to Cleft palate, psychomotor retardation, and distinctive facial features 616728; Multiple myeloma; ACTH-independent macronodular adrenal hyperplasia 3, MONDO:0700299
Mendeliome v1.4791 KDM1A Zornitza Stark Publications for gene: KDM1A were set to 29559475; 27094131
Mendeliome v1.4790 Zornitza Stark Added reviews for gene KDM1A from panel Primary nodular adrenocortical disease
Growth failure v1.104 MAU2 Zornitza Stark Phenotypes for gene: MAU2 were changed from Cornelia de Lange syndrome MONDO:0016033, MAU2-related to Cornelia de Lange syndrome 7, MIM# 621570
Growth failure v1.103 MAU2 Zornitza Stark reviewed gene: MAU2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 7, MIM# 621570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.757 MAU2 Zornitza Stark Phenotypes for gene: MAU2 were changed from Cornelia de Lange syndrome MONDO:0016033, MAU2-related to Cornelia de Lange syndrome 7, MIM# 621570
Intellectual disability syndromic and non-syndromic v1.756 MAU2 Zornitza Stark reviewed gene: MAU2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 7, MIM# 621570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.428 MAU2 Zornitza Stark Phenotypes for gene: MAU2 were changed from Cornelia de Lange syndrome MONDO:0016033, MAU2-related to Cornelia de Lange syndrome 7, MIM# 621570
Microcephaly v1.427 MAU2 Zornitza Stark reviewed gene: MAU2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 7, MIM# 621570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4789 MAU2 Zornitza Stark Phenotypes for gene: MAU2 were changed from Cornelia de Lange syndrome MONDO:0016033, MAU2-related to Cornelia de Lange syndrome 7, MIM# 621570
Mendeliome v1.4788 MAU2 Zornitza Stark reviewed gene: MAU2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 7, MIM# 621570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v1.55 RPL27 Zornitza Stark Phenotypes for gene: RPL27 were changed from Diamond-Blackfan anemia 16, MIM# 617408 to Diamond-Blackfan anaemia 16, MIM# 617408
Red cell disorders v1.54 RPL27 Zornitza Stark Publications for gene: RPL27 were set to 25424902
Red cell disorders v1.53 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
Red cell disorders v1.53 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Red cell disorders v1.52 RPL27 Zornitza Stark edited their review of gene: RPL27: Added comment: PMID 38988374 reports an individual from a second unrelated family with a de novo splice‑site RPL27 variant and a DBA phenotype.; Changed rating: AMBER; Changed publications: 25424902, 38988374; Changed phenotypes: Diamond-Blackfan anaemia 16, MIM# 617408
Diamond Blackfan anaemia v1.20 RPL27 Zornitza Stark Phenotypes for gene: RPL27 were changed from Diamond-Blackfan anemia 16, MIM# 617408 to Diamond-Blackfan anaemia 16, MIM# 617408
Mendeliome v1.4788 RPL27 Zornitza Stark Publications for gene: RPL27 were set to 25424902
Mendeliome v1.4787 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
Mendeliome v1.4787 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4786 RPL27 Zornitza Stark edited their review of gene: RPL27: Added comment: PMID 38988374 reports an individual from a second unrelated family with a de novo splice‑site RPL27 variant and a DBA phenotype.; Changed rating: AMBER; Changed publications: 25424902, 38988374
Bone Marrow Failure v1.144 RPL27 Zornitza Stark Phenotypes for gene: RPL27 were changed from Diamond-Blackfan anemia 16, MIM# 617408 to Diamond-Blackfan anaemia 16, MIM# 617408
Bone Marrow Failure v1.143 RPL27 Zornitza Stark Publications for gene: RPL27 were set to 25424902
Bone Marrow Failure v1.142 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
Bone Marrow Failure v1.142 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.141 RPL27 Zornitza Stark edited their review of gene: RPL27: Added comment: PMID 38988374 reports an individual from a second unrelated family with a de novo splice‑site RPL27 variant and a DBA phenotype.; Changed rating: AMBER; Changed publications: 25424902, 38988374; Changed phenotypes: Diamond-Blackfan anaemia 16, MIM# 617408
Diamond Blackfan anaemia v1.19 RPL27 Zornitza Stark Publications for gene: RPL27 were set to 25424902
Diamond Blackfan anaemia v1.18 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
Diamond Blackfan anaemia v1.18 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Diamond Blackfan anaemia v1.17 RPL27 Zornitza Stark edited their review of gene: RPL27: Added comment: PMID 38988374 reports an individual from a second unrelated family with a de novo splice‑site RPL27 variant and a DBA phenotype.; Changed rating: AMBER; Changed publications: 38988374; Changed phenotypes: Diamond-Blackfan anemia 16, MONDO:0044309; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4786 RPL4 Zornitza Stark Marked gene: RPL4 as ready
Mendeliome v1.4786 RPL4 Zornitza Stark Gene: rpl4 has been classified as Red List (Low Evidence).
Mendeliome v1.4786 Zornitza Stark Copied gene RPL4 from panel Diamond Blackfan anaemia
Mendeliome v1.4786 RPL4 Zornitza Stark gene: RPL4 was added
gene: RPL4 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RPL4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL4 were set to 30213830
Phenotypes for gene: RPL4 were set to Diamond Blackfan anaemia, MONDO:0015253, RPL4-related
Diamond Blackfan anaemia v1.17 RPL4 Zornitza Stark Marked gene: RPL4 as ready
Diamond Blackfan anaemia v1.17 RPL4 Zornitza Stark Gene: rpl4 has been classified as Red List (Low Evidence).
Diamond Blackfan anaemia v1.17 RPL4 Zornitza Stark gene: RPL4 was added
gene: RPL4 was added to Diamond Blackfan anaemia. Sources: Literature
Mode of inheritance for gene: RPL4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL4 were set to 30213830
Phenotypes for gene: RPL4 were set to Diamond Blackfan anaemia, MONDO:0015253, RPL4-related
Review for gene: RPL4 was set to RED
Added comment: PMID 30213830 reports a single individual with a de novo heterozygous splice‑site RPL4 variant presenting with Diamond‑Blackfan anemia‑like syndrome (macrocytic anemia, growth retardation, cleft lip, low‑set ears, toe anomalies, developmental delay, short stature, hearing loss). Functional assays show aberrant splicing, impaired ribosomal RNA processing, and somatic reversion via mosaic UPD15q, supporting loss‑of‑function haploinsufficiency.
Sources: Literature
Prepair 500+ v2.1 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Retinitis pigmentosa 59, MIM#613861; Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Congenital disorder of glycosylation, type 1bb, MIM# 621567
Prepair 500+ v2.0 DHDDS Zornitza Stark reviewed gene: DHDDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 621567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v2.17 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Retinitis pigmentosa 59, MIM#613861; Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Retinitis pigmentosa 59, MIM#613861; Congenital disorder of glycosylation, type 1bb, MIM# 621567
Prepair 1000+ v2.16 DHDDS Zornitza Stark reviewed gene: DHDDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 621567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.246 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Congenital disorder of glycosylation, type 1bb, MIM# 621567
Retinitis pigmentosa v0.245 DHDDS Zornitza Stark edited their review of gene: DHDDS: Changed phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 621567
Mendeliome v1.4785 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Developmental delay and seizures with or without movement abnormalities, MIM#617836; Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Developmental delay and seizures with or without movement abnormalities, MIM#617836; Congenital disorder of glycosylation, type 1bb, MIM# 621567
Mendeliome v1.4784 DHDDS Zornitza Stark edited their review of gene: DHDDS: Changed phenotypes: Developmental delay and seizures with or without movement abnormalities, MIM#617836, Congenital disorder of glycosylation, type 1bb, MIM# 621567
Congenital Disorders of Glycosylation v1.86 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Congenital disorder of glycosylation, type 1bb, MIM# 621567
Congenital Disorders of Glycosylation v1.85 DHDDS Zornitza Stark edited their review of gene: DHDDS: Changed phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 621567
Mendeliome v1.4784 HAT1 Monique Dunstan Tag SV/CNV was removed from gene: HAT1.
Tag STR was removed from gene: HAT1.
Tag refuted was removed from gene: HAT1.
Hereditary Pigmentary Disorders v1.5 ABCB6 Katrina Bell Deleted their review
Hereditary Pigmentary Disorders v1.5 ABCB6 Katrina Bell Deleted their comment
Stroke v1.48 ABCA1 Katrina Bell Deleted their review
Mendeliome v1.4784 HAT1 Monique Dunstan All sources for gene: HAT1 were removed
Mendeliome v1.4783 ABCA1 Katrina Bell Tag somatic was removed from gene: ABCA1.
Tag 5'UTR was removed from gene: ABCA1.
Mendeliome v1.4783 ABCA1 Katrina Bell Deleted their review
Mendeliome v1.4783 ABCA1 Katrina Bell Deleted their comment
Mendeliome v1.4783 ALG5 Monique Dunstan Deleted their review
Mendeliome v1.4783 HAT1 Monique Dunstan Deleted their review
Mendeliome v1.4783 HAT1 Monique Dunstan Deleted their comment
Mendeliome v1.4783 HAT1 Monique Dunstan Deleted their comment
Mendeliome v1.4783 ABCB6 Katrina Bell Deleted their review
Mendeliome v1.4783 ABCB6 Katrina Bell Deleted their comment
Intellectual disability syndromic and non-syndromic v1.756 CRMP1 Zornitza Stark Phenotypes for gene: CRMP1 were changed from neurodevelopmental disorder, MONDO:0700092, CRMP2-related to neurodevelopmental disorder, MONDO:0700092, CRMP1-related
Intellectual disability syndromic and non-syndromic v1.755 CRMP1 Zornitza Stark edited their review of gene: CRMP1: Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, CRMP1-related
Mendeliome v1.4783 CRMP1 Zornitza Stark Phenotypes for gene: CRMP1 were changed from neurodevelopmental disorder, MONDO:0700092, CRMP2-related to neurodevelopmental disorder, MONDO:0700092, CRMP1-related
Mendeliome v1.4782 CRMP1 Zornitza Stark edited their review of gene: CRMP1: Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, CRMP1-related
Genetic Epilepsy v1.410 RYR3 Lilian Downie Added comment: Comment on mode of inheritance: Limited by clingen for AD epilepsy, not considered for AR by ClinGen.
All of the recessive DEE patients are from the 2 Chinese papers PMID 39840699, PMID: 29667327. Amber for AR DEE
Genetic Epilepsy v1.410 RYR3 Lilian Downie Mode of inheritance for gene: RYR3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.409 RYR3 Lucy Spencer reviewed gene: RYR3: Rating: AMBER; Mode of pathogenicity: None; Publications: 39220738, 39840699, 25262651, 29667327, 31230720; Phenotypes: Developmental and epileptic encephalopathy MONDO:0100620, RYR3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.249 GNPNAT1 Zornitza Stark Publications for gene: GNPNAT1 were set to 36097642; 35427807; 32591345
Skeletal Dysplasia_Fetal v0.248 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.248 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Green List (High Evidence).
Fetal anomalies v1.567 GNPNAT1 Zornitza Stark Publications for gene: GNPNAT1 were set to 36097642; 35427807; 32591345
Fetal anomalies v1.566 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Green List (high evidence)
Fetal anomalies v1.566 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.247 Zornitza Stark Added reviews for gene GNPNAT1 from panel Skeletal dysplasia
Fetal anomalies v1.565 Zornitza Stark Added reviews for gene GNPNAT1 from panel Skeletal dysplasia
Skeletal dysplasia v0.433 GNPNAT1 Zornitza Stark Publications for gene: GNPNAT1 were set to 32591345
Skeletal dysplasia v0.432 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Green List (high evidence)
Skeletal dysplasia v0.432 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Green List (High Evidence).
Mendeliome v1.4782 GNPNAT1 Zornitza Stark Publications for gene: GNPNAT1 were set to 32591345
Mendeliome v1.4781 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Green List (high evidence)
Mendeliome v1.4781 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Green List (High Evidence).
Mendeliome v1.4780 GAS2L2 Zornitza Stark Publications for gene: GAS2L2 were set to 30665704
Mendeliome v1.4779 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Green List (high evidence)
Mendeliome v1.4779 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.77 GAS2L2 Zornitza Stark Publications for gene: GAS2L2 were set to 30665704
Ciliary Dyskinesia v1.76 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Green List (high evidence)
Ciliary Dyskinesia v1.76 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Green List (High Evidence).
Fetal anomalies v1.564 FRMD4A Zornitza Stark Marked gene: FRMD4A as ready
Fetal anomalies v1.564 FRMD4A Zornitza Stark Added comment: Comment when marking as ready: Note discrepancy in head size and predominance of missense variants, hence retain Amber rating.
Fetal anomalies v1.564 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.564 FRMD4A Zornitza Stark Publications for gene: FRMD4A were set to 30266093; 25388005; 30214071
Intellectual disability syndromic and non-syndromic v1.755 FRMD4A Zornitza Stark Marked gene: FRMD4A as ready
Intellectual disability syndromic and non-syndromic v1.755 FRMD4A Zornitza Stark Added comment: Comment when marking as ready: Note discordant phenotype in relation to head size and predominance of missense variants, hence retain Amber rating
Intellectual disability syndromic and non-syndromic v1.755 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.755 FRMD4A Zornitza Stark Publications for gene: FRMD4A were set to 25388005; 30214071
Intellectual disability syndromic and non-syndromic v1.754 Zornitza Stark Added reviews for gene FRMD4A from panel Mendeliome
Fetal anomalies v1.563 Zornitza Stark Added reviews for gene FRMD4A from panel Mendeliome
Mendeliome v1.4778 FRMD4A Zornitza Stark Marked gene: FRMD4A as ready
Mendeliome v1.4778 FRMD4A Zornitza Stark Added comment: Comment when marking as ready: Note phenotype is discordant in terms of head circumference and also evidence based on missense variants, retain Amber rating.
Mendeliome v1.4778 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4778 FRMD4A Zornitza Stark Publications for gene: FRMD4A were set to 25388005; 30214071
Fetal anomalies v1.562 FAM92A Zornitza Stark Publications for gene: FAM92A were set to 30395363
Fetal anomalies v1.561 FAM92A Zornitza Stark Classified gene: FAM92A as Green List (high evidence)
Fetal anomalies v1.561 FAM92A Zornitza Stark Gene: fam92a has been classified as Green List (High Evidence).
Fetal anomalies v1.560 Zornitza Stark Added reviews for gene FAM92A from panel Mendeliome
Polydactyly v0.303 FAM92A Zornitza Stark Publications for gene: FAM92A were set to 30395363
Polydactyly v0.302 FAM92A Zornitza Stark Classified gene: FAM92A as Green List (high evidence)
Polydactyly v0.302 FAM92A Zornitza Stark Gene: fam92a has been classified as Green List (High Evidence).
Mendeliome v1.4777 FAM92A Zornitza Stark Publications for gene: FAM92A were set to 30395363
Mendeliome v1.4776 FAM92A Zornitza Stark Classified gene: FAM92A as Green List (high evidence)
Mendeliome v1.4776 FAM92A Zornitza Stark Gene: fam92a has been classified as Green List (High Evidence).
Mendeliome v1.4775 FOXJ3 Rylee Peters Classified gene: FOXJ3 as Amber List (moderate evidence)
Mendeliome v1.4775 FOXJ3 Rylee Peters Gene: foxj3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4774 PLEKHM2 Rylee Peters Phenotypes for gene: PLEKHM2 were changed from Dilated cardiomyopathy MONDO:0005021 to Dilated cardiomyopathy, MONDO:0005021, PLEKHM2-related
Mendeliome v1.4773 PLEKHM2 Rylee Peters Publications for gene: PLEKHM2 were set to 35862026; 26464484; 38942823; 38490981; 37349842
Mendeliome v1.4772 MT-TQ Rylee Peters Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Mendeliome v1.4771 TRU-TCA1-1 Zornitza Stark Classified gene: TRU-TCA1-1 as Amber List (moderate evidence)
Mendeliome v1.4771 TRU-TCA1-1 Zornitza Stark Gene: tru-tca1-1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4770 SCP2 Zornitza Stark Phenotypes for gene: SCP2 were changed from Leukoencephalopathy with dystonia and motor neuropathy, MIM#613724 to Leukoencephalopathy with dystonia and motor neuropathy, MIM#613724; Craniofacial microsomia, MONDO:0015397, SCP2-related
Mendeliome v1.4769 SCP2 Zornitza Stark Publications for gene: SCP2 were set to 16685654; 26497993
Mendeliome v1.4768 SCP2 Zornitza Stark Mode of inheritance for gene: SCP2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v0.137 NLGN3 Chirag Patel Marked gene: NLGN3 as ready
Hypogonadotropic hypogonadism v0.137 NLGN3 Chirag Patel Gene: nlgn3 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.137 NLGN3 Chirag Patel Phenotypes for gene: NLGN3 were changed from X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425 to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425; Hypogonadotropic hypogonadism MONDO:0018555
Mendeliome v1.4767 SCP2 Zornitza Stark edited their review of gene: SCP2: Added comment: PMID 39941065 reports 2 individuals from 2 unrelated families with de novo heterozygous missense CTDSP2 (c.332C>A, p.T111N) variants presenting with hemifacial microsomia (unilateral facial hypoplasia, ear malformations, mandibular underdevelopment). Zebrafish ctdsp2 knockout recapitulates the craniofacial phenotype and rescue by wild‑type ctdsp2 mRNA or tp53 knockout restores normal cartilage, providing functional support.; Changed publications: 26497993, 39941065; Changed phenotypes: Leukoencephalopathy with dystonia and motor neuropathy, MIM#613724, Craniofacial microsomia, MONDO:0015397, SCP2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v0.136 NLGN3 Chirag Patel Mode of inheritance for gene: NLGN3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hypogonadotropic hypogonadism v0.135 NLGN3 Chirag Patel Classified gene: NLGN3 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v0.135 NLGN3 Chirag Patel Gene: nlgn3 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.134 Chirag Patel Added reviews for gene NLGN3 from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.226 NLGN3 Chirag Patel reviewed gene: NLGN3: Rating: AMBER; Mode of pathogenicity: None; Publications: 36810932; Phenotypes: Hypogonadotropic hypogonadism MONDO:0018555; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Pituitary hormone deficiency v0.226 NLGN3 Chirag Patel Marked gene: NLGN3 as ready
Pituitary hormone deficiency v0.226 NLGN3 Chirag Patel Gene: nlgn3 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.226 NLGN3 Chirag Patel Phenotypes for gene: NLGN3 were changed from X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425 to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425; hypogonadotropic hypogonadism MONDO:0018555
Pituitary hormone deficiency v0.225 NLGN3 Chirag Patel Classified gene: NLGN3 as Amber List (moderate evidence)
Pituitary hormone deficiency v0.225 NLGN3 Chirag Patel Gene: nlgn3 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.224 Chirag Patel Copied gene NLGN3 from panel Mendeliome
Pituitary hormone deficiency v0.224 NLGN3 Chirag Patel gene: NLGN3 was added
gene: NLGN3 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NLGN3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NLGN3 were set to 28584888; 12669065; 25167861
Phenotypes for gene: NLGN3 were set to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425
Hypogonadotropic hypogonadism v0.133 Chirag Patel Copied gene NLGN3 from panel Mendeliome
Hypogonadotropic hypogonadism v0.133 NLGN3 Chirag Patel gene: NLGN3 was added
gene: NLGN3 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NLGN3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NLGN3 were set to 28584888; 12669065; 25167861
Phenotypes for gene: NLGN3 were set to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425
Pituitary hormone deficiency v0.223 NEUROG3 Chirag Patel Marked gene: NEUROG3 as ready
Pituitary hormone deficiency v0.223 NEUROG3 Chirag Patel Gene: neurog3 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.223 Chirag Patel Copied gene NEUROG3 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.223 NEUROG3 Chirag Patel gene: NEUROG3 was added
gene: NEUROG3 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NEUROG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG3 were set to 36149814; 27533310
Phenotypes for gene: NEUROG3 were set to Congenital malabsorptive diarrhea 4, MONDO:0012479; Hypogonadotropic hypogonadism, MONDO:0018555
Hypogonadotropic hypogonadism v0.132 NEUROG3 Chirag Patel Classified gene: NEUROG3 as Green List (high evidence)
Hypogonadotropic hypogonadism v0.132 NEUROG3 Chirag Patel Gene: neurog3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.131 NEUROG3 Chirag Patel Marked gene: NEUROG3 as ready
Hypogonadotropic hypogonadism v0.131 NEUROG3 Chirag Patel Gene: neurog3 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.131 NEUROG3 Chirag Patel gene: NEUROG3 was added
gene: NEUROG3 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: NEUROG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG3 were set to 36149814; 27533310
Phenotypes for gene: NEUROG3 were set to Congenital malabsorptive diarrhea 4, MONDO:0012479; Hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: NEUROG3 was set to GREEN
Added comment: PMID 27533310 reports 4 individuals from 3 families with 2 different homozygous rare missense variants (p.L135P and p.R107S) in NEUROG3 presenting with hypogonadotropic hypogonadism, congenital malabsorptive diarrhea, neonatal diabetes and short stature. No functional studies.

PMID 36149814 describes 3 unrelated Thai patients with families with 2 different homozygous rare missense variants ((p.Thr124Arg and p.Arg95Pro) in NEUROG3 presenting with multiple pituitary hormone deficiencies (GH deficiency and hypogonadotropic hypogonadism). Luciferase reporter assay showing markedly reduced transcriptional activity for both variants and western blot confirmed protein expression, indicating loss‑of‑function.
Sources: Literature
Motor Neurone Disease v1.49 ERBB4 Zornitza Stark Classified gene: ERBB4 as Green List (high evidence)
Motor Neurone Disease v1.49 ERBB4 Zornitza Stark Gene: erbb4 has been classified as Green List (High Evidence).
Mendeliome v1.4767 ERBB4 Zornitza Stark Classified gene: ERBB4 as Green List (high evidence)
Mendeliome v1.4767 ERBB4 Zornitza Stark Gene: erbb4 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.130 LEPR Chirag Patel Marked gene: LEPR as ready
Hypogonadotropic hypogonadism v0.130 LEPR Chirag Patel Gene: lepr has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.130 LEPR Chirag Patel Phenotypes for gene: LEPR were changed from Obesity, morbid, due to leptin receptor deficiency (MIM#614963) to Obesity due to leptin receptor gene deficiency, MONDO:0013992
Hypogonadotropic hypogonadism v0.129 LEPR Chirag Patel Publications for gene: LEPR were set to 17229951; 29545012
Hypogonadotropic hypogonadism v0.128 Chirag Patel Added reviews for gene LEPR from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.222 LEPR Chirag Patel Phenotypes for gene: LEPR were changed from Obesity, morbid, due to leptin receptor deficiency (MIM#614963) to Obesity due to leptin receptor gene deficiency, MONDO:0013992
Pituitary hormone deficiency v0.221 LEPR Chirag Patel Marked gene: LEPR as ready
Pituitary hormone deficiency v0.221 LEPR Chirag Patel Gene: lepr has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.221 LEPR Chirag Patel Publications for gene: LEPR were set to 17229951; 29545012
Pituitary hormone deficiency v0.220 LEPR Chirag Patel reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 31658438; Phenotypes: Obesity due to leptin receptor gene deficiency, MONDO:0013992; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.220 Chirag Patel Copied gene LEPR from panel Mendeliome
Pituitary hormone deficiency v0.220 LEPR Chirag Patel gene: LEPR was added
gene: LEPR was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
treatable, clinical trial tags were added to gene: LEPR.
Mode of inheritance for gene: LEPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LEPR were set to 17229951; 29545012
Phenotypes for gene: LEPR were set to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Hypogonadotropic hypogonadism v0.127 Chirag Patel Copied gene LEPR from panel Mendeliome
Hypogonadotropic hypogonadism v0.127 LEPR Chirag Patel gene: LEPR was added
gene: LEPR was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Victorian Clinical Genetics Services
treatable, clinical trial tags were added to gene: LEPR.
Mode of inheritance for gene: LEPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LEPR were set to 17229951; 29545012
Phenotypes for gene: LEPR were set to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Pituitary hormone deficiency v0.219 TBX3 Chirag Patel Marked gene: TBX3 as ready
Pituitary hormone deficiency v0.219 TBX3 Chirag Patel Gene: tbx3 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.219 TBX3 Chirag Patel Publications for gene: TBX3 were set to 9207801; 19938096; 28145909
Pituitary hormone deficiency v0.218 Chirag Patel Added reviews for gene TBX3 from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.126 TBX3 Chirag Patel Marked gene: TBX3 as ready
Hypogonadotropic hypogonadism v0.126 TBX3 Chirag Patel Gene: tbx3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.126 TBX3 Chirag Patel Publications for gene: TBX3 were set to 9207801; 19938096; 28145909
Hypogonadotropic hypogonadism v0.125 TBX3 Chirag Patel reviewed gene: TBX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40485890, 39788453, 36937985, 30550377; Phenotypes: Ulnar-mammary syndrome, MONDO:0008411; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.217 Chirag Patel Copied gene TBX3 from panel Radial Ray Abnormalities
Pituitary hormone deficiency v0.217 TBX3 Chirag Patel gene: TBX3 was added
gene: TBX3 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TBX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX3 were set to 9207801; 19938096; 28145909
Phenotypes for gene: TBX3 were set to Ulnar-mammary syndrome, MIM# 181450; MONDO:0008411
Hypogonadotropic hypogonadism v0.125 Chirag Patel Copied gene TBX3 from panel Radial Ray Abnormalities
Hypogonadotropic hypogonadism v0.125 TBX3 Chirag Patel gene: TBX3 was added
gene: TBX3 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TBX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX3 were set to 9207801; 19938096; 28145909
Phenotypes for gene: TBX3 were set to Ulnar-mammary syndrome, MIM# 181450; MONDO:0008411
Polymicrogyria and Schizencephaly v0.207 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.207 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.207 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.207 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Publications for gene: TUBB3 were set to
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Marked gene: TUBB3 as ready
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Gene: tubb3 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Mode of inheritance for gene: TUBB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.205 Chirag Patel Added reviews for gene TUBB3 from panel Tubulinopathies
Pituitary hormone deficiency v0.216 TUBB3 Chirag Patel Marked gene: TUBB3 as ready
Pituitary hormone deficiency v0.216 TUBB3 Chirag Patel Gene: tubb3 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.216 Chirag Patel Copied gene TUBB3 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.216 TUBB3 Chirag Patel gene: TUBB3 was added
gene: TUBB3 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TUBB3 were set to 34652576; 25559402
Phenotypes for gene: TUBB3 were set to TUBB3-related tubulinopathy, MONDO:0100154
Hypogonadotropic hypogonadism v0.124 TUBB3 Chirag Patel Classified gene: TUBB3 as Green List (high evidence)
Hypogonadotropic hypogonadism v0.124 TUBB3 Chirag Patel Gene: tubb3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.123 TUBB3 Chirag Patel Marked gene: TUBB3 as ready
Hypogonadotropic hypogonadism v0.123 TUBB3 Chirag Patel Gene: tubb3 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.123 TUBB3 Chirag Patel gene: TUBB3 was added
gene: TUBB3 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TUBB3 were set to 34652576; 25559402
Phenotypes for gene: TUBB3 were set to TUBB3-related tubulinopathy, MONDO:0100154
Review for gene: TUBB3 was set to GREEN
Added comment: PMID 34652576 reports 14 individuals from 13 unrelated families with the same heterozygous de novo TUBB3 rare missense variant (p.Arg262His) presenting with congenital fibrosis of the extraocular muscles (CFEOM3), facial weakness, distal contractures, early‑onset peripheral neuropathy, and Kallmann syndrome (hypogonadotropic hypogonadism with anosmia). Detailed phenotyping and functional assays show dominant altered‑function of the mutant tubulin.

PMID 25559402 reports 4 affected individuals from 1 family (mother and 3 sons) with heterozygous TUBB3 rare missense variant (p.E410K) showing CFEOM, facial weakness, developmental delay, and variable endocrine abnormalities including hypogonadotropic hypogonadism, growth‑hormone deficiency and possible hypothyroidism. No functional data.
Sources: Literature
Pituitary hormone deficiency v0.215 POU6F2 Chirag Patel Marked gene: POU6F2 as ready
Pituitary hormone deficiency v0.215 POU6F2 Chirag Patel Gene: pou6f2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4766 POU6F2 Chirag Patel Publications for gene: POU6F2 were set to
Mendeliome v1.4765 POU6F2 Chirag Patel Phenotypes for gene: POU6F2 were changed from to Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.4764 POU6F2 Chirag Patel Mode of inheritance for gene: POU6F2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4763 POU6F2 Chirag Patel Classified gene: POU6F2 as Amber List (moderate evidence)
Mendeliome v1.4763 POU6F2 Chirag Patel Gene: pou6f2 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.215 Chirag Patel Copied gene POU6F2 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.215 POU6F2 Chirag Patel gene: POU6F2 was added
gene: POU6F2 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: POU6F2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POU6F2 were set to 37600690
Phenotypes for gene: POU6F2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.4762 Chirag Patel Added reviews for gene POU6F2 from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.122 POU6F2 Chirag Patel Marked gene: POU6F2 as ready
Hypogonadotropic hypogonadism v0.122 POU6F2 Chirag Patel Gene: pou6f2 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.122 POU6F2 Chirag Patel Classified gene: POU6F2 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v0.122 POU6F2 Chirag Patel Gene: pou6f2 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.121 POU6F2 Chirag Patel gene: POU6F2 was added
gene: POU6F2 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: POU6F2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POU6F2 were set to 37600690
Phenotypes for gene: POU6F2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: POU6F2 was set to AMBER
Added comment: PMID 37600690 reports 15 individuals from 12 unrelated families with idiopathic hypogonadotropic hypogonadism (IHH). Twelve rare missense variants in functional POU domains were identified. Inheritance includes autosomal recessive (Family‑A homozygous, p.Gly601Arg variant), autosomal dominant with variable penetrance, and a de novo case (Family‑I). All variants were classified as VUS. Functional assays in a human GnRH cell line showed the p.Gly601Arg variant abolished repression of GNRH1, supporting loss‑of‑function as the disease mechanism. The p.Asn629His variant (2 families) was common the Turkish population and had no effect on functional assays.
Sources: Literature
Hypogonadotropic hypogonadism v0.120 RNF216 Chirag Patel Marked gene: RNF216 as ready
Hypogonadotropic hypogonadism v0.120 RNF216 Chirag Patel Gene: rnf216 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.214 RNF216 Chirag Patel Marked gene: RNF216 as ready
Pituitary hormone deficiency v0.214 RNF216 Chirag Patel Gene: rnf216 has been classified as Green List (High Evidence).
Mendeliome v1.4761 RNF216 Chirag Patel Phenotypes for gene: RNF216 were changed from Cerebellar ataxia and hypogonadotropic hypogonadism MIM#212840 to Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Mendeliome v1.4760 RNF216 Chirag Patel Publications for gene: RNF216 were set to 23656588
Pituitary hormone deficiency v0.214 Chirag Patel Copied gene RNF216 from panel Differences of Sex Development
Pituitary hormone deficiency v0.214 RNF216 Chirag Patel gene: RNF216 was added
gene: RNF216 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF216 were set to 25841028; 23656588; 38050071
Phenotypes for gene: RNF216 were set to Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Mendeliome v1.4759 Chirag Patel Added reviews for gene RNF216 from panel Differences of Sex Development
Hypogonadotropic hypogonadism v0.120 Chirag Patel Copied gene RNF216 from panel Differences of Sex Development
Hypogonadotropic hypogonadism v0.120 RNF216 Chirag Patel gene: RNF216 was added
gene: RNF216 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF216 were set to 25841028; 23656588; 38050071
Phenotypes for gene: RNF216 were set to Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Differences of Sex Development v1.52 RNF216 Chirag Patel Phenotypes for gene: RNF216 were changed from Cerebellar ataxia and hypogonadotropic hypogonadism, MIM# 212840 to Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Differences of Sex Development v1.51 RNF216 Chirag Patel Publications for gene: RNF216 were set to 25841028; 23656588; 38050071
Differences of Sex Development v1.51 RNF216 Chirag Patel Publications for gene: RNF216 were set to 25841028; 23656588
Differences of Sex Development v1.50 RNF216 Chirag Patel reviewed gene: RNF216: Rating: GREEN; Mode of pathogenicity: None; Publications: 38050071; Phenotypes: Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.213 PLXNB1 Chirag Patel Marked gene: PLXNB1 as ready
Pituitary hormone deficiency v0.213 PLXNB1 Chirag Patel Gene: plxnb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4758 PLXNB1 Chirag Patel Marked gene: PLXNB1 as ready
Mendeliome v1.4758 PLXNB1 Chirag Patel Gene: plxnb1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.213 Chirag Patel Copied gene PLXNB1 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.213 PLXNB1 Chirag Patel gene: PLXNB1 was added
gene: PLXNB1 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PLXNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNB1 were set to 35170806
Phenotypes for gene: PLXNB1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Mendeliome v1.4758 Chirag Patel Copied gene PLXNB1 from panel Hypogonadotropic hypogonadism
Mendeliome v1.4758 PLXNB1 Chirag Patel gene: PLXNB1 was added
gene: PLXNB1 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PLXNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNB1 were set to 35170806
Phenotypes for gene: PLXNB1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Hypogonadotropic hypogonadism v0.119 PLXNB1 Chirag Patel Marked gene: PLXNB1 as ready
Hypogonadotropic hypogonadism v0.119 PLXNB1 Chirag Patel Gene: plxnb1 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.119 PLXNB1 Chirag Patel Classified gene: PLXNB1 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v0.119 PLXNB1 Chirag Patel Gene: plxnb1 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.118 PLXNB1 Chirag Patel gene: PLXNB1 was added
gene: PLXNB1 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: PLXNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNB1 were set to 35170806
Phenotypes for gene: PLXNB1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Review for gene: PLXNB1 was set to AMBER
Added comment: 6 individuals from 6 unrelated families with 6 different heterozygous missense PLXNB1 variants presenting with normosmic idiopathic hypogonadotropic hypogonadism (delayed puberty, low LH/FSH, normal olfaction). All variants were rare but classified as VUS (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, p.C1318R). 3 variants were inherited from an unaffected parent, but parental status could not be clarified for 3 variants could not be clarified. Functional assay of p.R1031H variant showed reduced membrane expression and impaired GnRH‑cell migration, supporting a dominant‑negative mechanism.
Sources: Literature
Pituitary hormone deficiency v0.212 SMCHD1 Chirag Patel Publications for gene: SMCHD1 were set to 28067909
Pituitary hormone deficiency v0.211 SMCHD1 Chirag Patel Marked gene: SMCHD1 as ready
Pituitary hormone deficiency v0.211 SMCHD1 Chirag Patel Gene: smchd1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.211 Chirag Patel Added reviews for gene SMCHD1 from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.117 SMCHD1 Chirag Patel Marked gene: SMCHD1 as ready
Hypogonadotropic hypogonadism v0.117 SMCHD1 Chirag Patel Gene: smchd1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.117 SMCHD1 Chirag Patel Publications for gene: SMCHD1 were set to 28067909
Hypogonadotropic hypogonadism v0.116 SMCHD1 Chirag Patel reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28067909, 38808953; Phenotypes: Arhinia, choanal atresia, microphthalmia MONDO:0011323; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.210 Chirag Patel Copied gene SMCHD1 from panel Choanal atresia
Pituitary hormone deficiency v0.210 SMCHD1 Chirag Patel gene: SMCHD1 was added
gene: SMCHD1 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SMCHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMCHD1 were set to 28067909
Phenotypes for gene: SMCHD1 were set to Bosma arhinia microphthalmia syndrome, MIM# 603457; Arhinia, choanal atresia, microphthalmia MONDO:0011323
Mode of pathogenicity for gene: SMCHD1 was set to Other
Hypogonadotropic hypogonadism v0.116 Chirag Patel Copied gene SMCHD1 from panel Choanal atresia
Hypogonadotropic hypogonadism v0.116 SMCHD1 Chirag Patel gene: SMCHD1 was added
gene: SMCHD1 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SMCHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMCHD1 were set to 28067909
Phenotypes for gene: SMCHD1 were set to Bosma arhinia microphthalmia syndrome, MIM# 603457; Arhinia, choanal atresia, microphthalmia MONDO:0011323
Mode of pathogenicity for gene: SMCHD1 was set to Other
Pituitary hormone deficiency v0.209 DLG2 Chirag Patel Marked gene: DLG2 as ready
Pituitary hormone deficiency v0.209 DLG2 Chirag Patel Gene: dlg2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.209 Chirag Patel Copied gene DLG2 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.209 DLG2 Chirag Patel gene: DLG2 was added
gene: DLG2 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Literature
SV/CNV tags were added to gene: DLG2.
Mode of inheritance for gene: DLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLG2 were set to 32341572
Phenotypes for gene: DLG2 were set to delayed puberty, self-limited, MONDO:0859205
Hypertrophic cardiomyopathy v1.25 POPDC2 Achchuthan Shanmugasundram reviewed gene: POPDC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41456958; Phenotypes: Cardiac conduction disease with or without cardiomyopathy 2, OMIM:621367; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.431 Sarah Milton Copied Region SHOX downstream regulatory region from panel Mendeliome
Skeletal dysplasia v0.431 SHOX downstream regulatory region Sarah Milton Region: SHOX downstream regulatory region was added
Region: SHOX downstream regulatory region was added to Skeletal dysplasia. Sources: Literature
regulatory region tags were added to Region: SHOX downstream regulatory region.
Mode of inheritance for Region: SHOX downstream regulatory region 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 Region: SHOX downstream regulatory region were set to PMID: 30250174; 22791839; 23636926; 20301394
Phenotypes for Region: SHOX downstream regulatory region were set to Leri-Weill dyschondrosteosis (MIM#127300); Short stature, idiopathic familial (MIM#300582)
Penetrance for Region: SHOX downstream regulatory region were set to Incomplete
Radial Ray Abnormalities v1.22 Sarah Milton Copied Region SHOX downstream regulatory region from panel Mendeliome
Radial Ray Abnormalities v1.22 SHOX downstream regulatory region Sarah Milton Region: SHOX downstream regulatory region was added
Region: SHOX downstream regulatory region was added to Radial Ray Abnormalities. Sources: Literature
regulatory region tags were added to Region: SHOX downstream regulatory region.
Mode of inheritance for Region: SHOX downstream regulatory region 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 Region: SHOX downstream regulatory region were set to PMID: 30250174; 22791839; 23636926; 20301394
Phenotypes for Region: SHOX downstream regulatory region were set to Leri-Weill dyschondrosteosis (MIM#127300); Short stature, idiopathic familial (MIM#300582)
Penetrance for Region: SHOX downstream regulatory region were set to Incomplete
Growth failure v1.103 Sarah Milton Copied Region SHOX downstream regulatory region from panel Mendeliome
Growth failure v1.103 SHOX downstream regulatory region Sarah Milton Region: SHOX downstream regulatory region was added
Region: SHOX downstream regulatory region was added to Growth failure. Sources: Literature
regulatory region tags were added to Region: SHOX downstream regulatory region.
Mode of inheritance for Region: SHOX downstream regulatory region 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 Region: SHOX downstream regulatory region were set to PMID: 30250174; 22791839; 23636926; 20301394
Phenotypes for Region: SHOX downstream regulatory region were set to Leri-Weill dyschondrosteosis (MIM#127300); Short stature, idiopathic familial (MIM#300582)
Penetrance for Region: SHOX downstream regulatory region were set to Incomplete
Mendeliome v1.4757 SHOX downstream regulatory region Sarah Milton Region: SHOX downstream regulatory region was added
Region: SHOX downstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: SHOX downstream regulatory region.
Mode of inheritance for Region: SHOX downstream regulatory region 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 Region: SHOX downstream regulatory region were set to PMID: 30250174; 22791839; 23636926; 20301394
Phenotypes for Region: SHOX downstream regulatory region were set to Leri-Weill dyschondrosteosis (MIM#127300); Short stature, idiopathic familial (MIM#300582)
Penetrance for Region: SHOX downstream regulatory region were set to Incomplete
Review for Region: SHOX downstream regulatory region was set to GREEN
Added comment: Deletions downstream of the SHOX coding region are known to be associated with idiopathic short stature and Leri-Weill dyschondrosteosis.

These deletions affect a conserved non coding element.
A recurrent 47.5kb deletion has been identified in a number of individuals with highly variable severity ranging from unaffected to Madelung deformity, short stature and mesomelia.

Supportive luciferase reporter assays in animal models confirm limb enhancer activity of this region.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.148 SPATA16 Zornitza Stark Publications for gene: SPATA16 were set to 17847006; 27086357; 29065458
Infertility and Recurrent Pregnancy Loss v1.147 SPATA16 Zornitza Stark Classified gene: SPATA16 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.147 SPATA16 Zornitza Stark Gene: spata16 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.146 SPATA16 Zornitza Stark reviewed gene: SPATA16: Rating: GREEN; Mode of pathogenicity: None; Publications: 30912172, 33877510, 39045326, 40376536; Phenotypes: Spermatogenic failure 6 MIM#102530, Spermatogenic failure 6 MONDO:0007060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4756 SPATA16 Zornitza Stark Publications for gene: SPATA16 were set to 17847006; 27086357; 29065458
Mendeliome v1.4755 SPATA16 Zornitza Stark Classified gene: SPATA16 as Green List (high evidence)
Mendeliome v1.4755 SPATA16 Zornitza Stark Gene: spata16 has been classified as Green List (High Evidence).
Mendeliome v1.4754 SPATA16 Zornitza Stark reviewed gene: SPATA16: Rating: GREEN; Mode of pathogenicity: None; Publications: 40376536, 39045326, 33877510, 30912172; Phenotypes: spermatogenic failure 6, MONDO:0007060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4754 MT-TQ Rylee Peters reviewed gene: MT-TQ: Rating: AMBER; Mode of pathogenicity: None; Publications: 38730005, 32588991; Phenotypes: Mitochondrial disease (MONDO:0044970), MT-TQ-related; Mode of inheritance: MITOCHONDRIAL
Fetal anomalies v1.559 PAK2 Elena Savva gene: PAK2 was added
gene: PAK2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAK2 were set to PMID: 39994693
Phenotypes for gene: PAK2 were set to ?Knobloch syndrome 2 MIM#618458
Review for gene: PAK2 was set to AMBER
Added comment: Domenach (2025): bilateral pleural effusion/chylothorax in a fetus at 24 weeks. Lit review notes an additional 2/5 probands with pleural effusion (1 also having chylothorax)
Sources: Literature
Congenital Heart Defect v0.535 PAK2 Elena Savva gene: PAK2 was added
gene: PAK2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAK2 were set to PMID: 38894571
Phenotypes for gene: PAK2 were set to ?Knobloch syndrome 2 MIM#618458
Review for gene: PAK2 was set to GREEN
Added comment: Additional patients in Schnur 2024 have some CHD, including PDA, ASD, VSD
Sources: Literature
Syndromic Retinopathy v0.257 PAK2 Elena Savva gene: PAK2 was added
gene: PAK2 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAK2 were set to PMID: 38894571
Phenotypes for gene: PAK2 were set to Knobloch syndrome 2 MIM#618458
Review for gene: PAK2 was set to GREEN
Added comment: Additional patients in Schnur 2024 have retinal detachment/retinopathy, described in 4/4 probands with de novo missense, one of which had an additional inherited chromosomal abnormality.
Sources: Literature
Genetic Epilepsy v1.409 PAK2 Elena Savva reviewed gene: PAK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40247748; Phenotypes: ?Knobloch syndrome 2 MIM#618458; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4754 PLEKHM2 Rylee Peters reviewed gene: PLEKHM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 40054934; Phenotypes: Dilated cardiomyopathy, MONDO:0005021, PLEKHM2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4754 NSMCE3 Rylee Peters reviewed gene: NSMCE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40728043, 33741030, 27427983; Phenotypes: Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: ICoNS v0.39 ALPL Lilian Downie Marked gene: ALPL as ready
Genomic newborn screening: ICoNS v0.39 ALPL Lilian Downie Gene: alpl has been classified as Red List (Low Evidence).
Genomic newborn screening: ICoNS v0.39 ALPL José Manuel González de Aledo Castillo reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genomic newborn screening: ICoNS v0.39 CD3D Lilian Downie gene: CD3D was added
gene: CD3D was added to Genomic newborn screening: ICoNS. Sources: Expert List
Mode of inheritance for gene: CD3D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD3D were set to PMID: 38022338, 36944331, 15729559, 16672702, https://doi.org/10.1016/j.jaci.2022.10.022
Phenotypes for gene: CD3D were set to primary immunodeficiency; life-threatening infections: recurrent bacterial/viral/ fungal infections; chronic diarrhoea; recurrent respiratory infections; failure to thrive. Immunologic profile shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype.; OMIM: 186790
Added comment: Gene is in Baby Detect (Liege, Belgium) gene panel
Sources: Expert List
Genomic newborn screening: ICoNS v0.38 RPS26 Lilian Downie Marked gene: RPS26 as ready
Genomic newborn screening: ICoNS v0.38 RPS26 Lilian Downie Gene: rps26 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.38 RPS26 Lilian Downie Classified gene: RPS26 as Green List (high evidence)
Genomic newborn screening: ICoNS v0.38 RPS26 Lilian Downie Gene: rps26 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Marked gene: RPS19 as ready
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Gene: rps19 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Classified gene: RPS19 as Green List (high evidence)
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Added comment: Comment on list classification: Some challenges identifying variants; deep intronic, large deletions reported
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Gene: rps19 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.36 RPS19 Jorune Balciuniene changed review comment from: Accounts for 25-30% of all DBA.
Penetrance seems to be high but incomplete with variable expressivity. Missense variants are less penetrant

More than 90% of the patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation; to: Accounts for 25-30% of all DBA.
Penetrance seems to be high but incomplete with variable expressivity. Missense variants are less penetrant.

Genetic testing complexities: Deep intronic pathogenic variant c.172+350C>T

More than 90% of the patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Genomic newborn screening: ICoNS v0.36 ALPL Lilian Downie gene: ALPL was added
gene: ALPL was added to Genomic newborn screening: ICoNS. Sources: Expert List
Mode of inheritance for gene: ALPL was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: ClinGen
ALPL is curated by the ClinGen Skeletal Disorders Gene Curation Expert Panel and has Definitive gene–disease validity for both ALPL-related autosomal recessive hypophosphatasia and ALPL-related autosomal dominant hypophosphatasia.
Treatment
Enzyme replacement therapy (ERT) for avoiding/reducing respiratory failure leading to long-term ventilatory support or death and for rickets or fractures, and also avoidance of bisphosphonates as a management consideration.
Asfotase alfa (ERT) improves pulmonary function, bone health and calcium homeostasis, and survival in infantile and early childhood hypophosphatasia.
Asfotase alfa improved survival in perinatal/infantile hypophosphatasia versus historical controls, with survival reported as 95% vs 42% at age 1 year and 84% vs 27% at age 5 years. Also marked benefit among treated patients needing respiratory support has been reported.
Genomic newborn screening challenges
The main genomic-screening challenge is the extreme phenotype spectrum: ALPL can cause perinatal lethal, infantile, childhood, adult, and odontohypophosphatasia presentations, and both AR and AD inheritance occur. Dominant-negative effects have been described in some autosomal dominant cases.
Another major issue is reduced penetrance/variable expressivity, especially for heterozygous ALPL variants. Penetrance in adult heterozygotes is low or incompletely understood
Variants of interest
The ALPL field has created a dedicated international variant-classification project and database
https://alplmutationdatabase.jku.at/
At the gene level, ALPL has more than 440 reported variants, including missense, nonsense, splice-site, small deletion/insertion, and other disruptive variants. Missense variants are common. Rather than a small number of recurrent variants, ALPL is characterized by broad allelic heterogeneity, with both loss-of-function and dominant-negative missense variants contributing to disease.
Genomic newborn screening inclusion
Included in most genomic newborn screening programs, but some of them just the recessive form
Traditional newborn screening
Hypophosphatasia is not part of standard routine traditional newborn screening panels. There is a pilot biochemical newborn screening study from Kumamoto Prefecture, Japan, which the authors describe as the first study on newborn screening for HPP worldwide. It used dried blood spots to measure TNAP (tissue-nonspecific alkaline phosphatase) activity in 45,632 newborns and identified one child who later showed HPP-related manifestations.
Sources: Expert List
Craniosynostosis v1.85 ARSB Judit Garcia reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 17458871, 30118150, 34948256; Phenotypes: Mucopolysaccharidosis type VI (Maroteaux-Lamy), MIM# 253200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genomic newborn screening: ICoNS v0.35 RPS26 Jorune Balciuniene gene: RPS26 was added
gene: RPS26 was added to Genomic newborn screening: ICoNS. Sources: Literature
Mode of inheritance for gene: RPS26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS26 were set to 20301769, 30503522
Phenotypes for gene: RPS26 were set to Diamond-Blackfan anemia 10
Penetrance for gene: RPS26 were set to unknown
Review for gene: RPS26 was set to GREEN
Added comment: Accounts for 6-9% of all DBA.
Penetrance high, variable expressivity

More than 90% of DBA patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: Literature
Genomic newborn screening: ICoNS v0.35 RPS24 Jorune Balciuniene gene: RPS24 was added
gene: RPS24 was added to Genomic newborn screening: ICoNS. Sources: Literature
Mode of inheritance for gene: RPS24 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS24 were set to 39568018, 17186470, 25946618
Phenotypes for gene: RPS24 were set to Diamond-blackfan anemia 3
Penetrance for gene: RPS24 were set to unknown
Review for gene: RPS24 was set to GREEN
Added comment: Accounts for 2-3% of all DBA.

More than 90% of DBA patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: Literature
Genomic newborn screening: ICoNS v0.35 RPS17 Jorune Balciuniene gene: RPS17 was added
gene: RPS17 was added to Genomic newborn screening: ICoNS. Sources: ClinGen,Literature
Mode of inheritance for gene: RPS17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS17 were set to 20301769
Phenotypes for gene: RPS17 were set to Diamond-Blackfan anemia 4
Penetrance for gene: RPS17 were set to unknown
Review for gene: RPS17 was set to GREEN
gene: RPS17 was marked as current diagnostic
Added comment: Accounts for 1-3% of all DBA.
Penetrance seems high, variable expressivity.

More than 90% of DBA patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: ClinGen, Literature
Genomic newborn screening: ICoNS v0.35 RPL5 Jorune Balciuniene gene: RPL5 was added
gene: RPL5 was added to Genomic newborn screening: ICoNS. Sources: ClinGen,Literature
Mode of inheritance for gene: RPL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL5 were set to 19773262
Phenotypes for gene: RPL5 were set to Diamond-Blackfan anemia 6
Penetrance for gene: RPL5 were set to Incomplete
Review for gene: RPL5 was set to GREEN
gene: RPL5 was marked as current diagnostic
Added comment: Accounts for 7-12% of all DBA.
Penetrance seems to be high but incomplete with variable expressivity. Manifestation often include small gestational age, craniofacial, congenital heart, and thumb defects.

More than 90% of DBA patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: ClinGen, Literature
Genomic newborn screening: ICoNS v0.35 RPS19 Jorune Balciuniene edited their review of gene: RPS19: Added comment: Accounts for 25-30% of all DBA.
Penetrance seems to be high but incomplete with variable expressivity. Missense variants are less penetrant

More than 90% of the patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation; Set current diagnostic: yes
Genomic newborn screening: ICoNS v0.35 RPL11 Jorune Balciuniene gene: RPL11 was added
gene: RPL11 was added to Genomic newborn screening: ICoNS. Sources: Literature
Mode of inheritance for gene: RPL11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL11 were set to 19773262, 20301769
Phenotypes for gene: RPL11 were set to Diamond-Blackfan anemia 7
Penetrance for gene: RPL11 were set to Incomplete
Review for gene: RPL11 was set to GREEN
gene: RPL11 was marked as current diagnostic
Added comment: Accounts for 5%-7% of all DBA.
Pathogenic variants in RPL11 are predominantly associated with thumb abnormalities. Penetrance seems to be high but incomplete (a couple of families with asymptomatic parents reported) with variable expressivity

More than 90% of the patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: Literature
Severe Combined Immunodeficiency v1.30 CD3D Kristina Hovhannesyan reviewed gene: CD3D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38022338, 36944331, 15729559, 16672702, https://doi.org/10.1016/j.jaci.2022.10.022; Phenotypes: primary immunodeficiency, life-threatening infections: recurrent bacterial/viral/ fungal infections, chronic diarrhoea, recurrent respiratory infections, failure to thrive. Immunologic profile shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype., OMIM: 186790; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe early-onset obesity v1.32 MRAP2 Zornitza Stark Publications for gene: MRAP2 were set to 23869016; 31700171; 27474872; 26795956
Severe early-onset obesity v1.31 MRAP2 Zornitza Stark Classified gene: MRAP2 as Green List (high evidence)
Severe early-onset obesity v1.31 MRAP2 Zornitza Stark Gene: mrap2 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.30 MRAP2 Zornitza Stark edited their review of gene: MRAP2: Added comment: Multiple studies PMIDs 31700171, 27474872, 37888144, 40822950, 29704154, 39574659a report 31 individuals from 13 unrelated families carrying heterozygous loss‑of‑function MRAP2 variants that cause early‑onset severe obesity, hyperphagia, hypertension and hyperglycaemia. Functional assays in CHO and HEK293 cells demonstrate reduced MC4R/MC3R‑dependent cAMP signaling, supporting a loss‑of‑function mechanism.; Changed rating: GREEN; Changed publications: 40822950, 39574659, 37888144, 33026327, 31700171, 29704154, 27474872
Mendeliome v1.4754 MRAP2 Zornitza Stark Publications for gene: MRAP2 were set to 23869016; 31700171; 27474872; 26795956
Mendeliome v1.4753 MRAP2 Zornitza Stark Classified gene: MRAP2 as Green List (high evidence)
Mendeliome v1.4753 MRAP2 Zornitza Stark Gene: mrap2 has been classified as Green List (High Evidence).
Mendeliome v1.4752 MRAP2 Zornitza Stark edited their review of gene: MRAP2: Added comment: Multiple studies PMIDs 31700171, 27474872, 37888144, 40822950, 29704154, 39574659a report 31 individuals from 13 unrelated families carrying heterozygous loss‑of‑function MRAP2 variants that cause early‑onset severe obesity, hyperphagia, hypertension and hyperglycaemia. Functional assays in CHO and HEK293 cells demonstrate reduced MC4R/MC3R‑dependent cAMP signaling, supporting a loss‑of‑function mechanism.; Changed rating: GREEN; Changed publications: 40822950, 39574659, 37888144, 33026327, 31700171, 29704154, 27474872; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Infertility and Recurrent Pregnancy Loss v1.146 MOV10L1 Zornitza Stark Marked gene: MOV10L1 as ready
Infertility and Recurrent Pregnancy Loss v1.146 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.146 MOV10L1 Zornitza Stark Publications for gene: MOV10L1 were set to 35476666; 20534472
Infertility and Recurrent Pregnancy Loss v1.145 MOV10L1 Zornitza Stark Classified gene: MOV10L1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.145 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.144 MOV10L1 Zornitza Stark edited their review of gene: MOV10L1: Added comment: PMIDs 35413094 and 39122675 report five individuals from five unrelated families with biallelic MOV10L1 variants presenting with non‑obstructive azoospermia due to spermatogenic failure (maturation arrest). Immunohistochemistry, minigene splicing assays, and piRNA‑seq demonstrate loss of MOV10L1 expression and disrupted piRNA biogenesis, supporting pathogenicity.; Changed rating: GREEN; Changed publications: 35476666, 20534472, 39122675
Mendeliome v1.4752 MOV10L1 Zornitza Stark Classified gene: MOV10L1 as Green List (high evidence)
Mendeliome v1.4752 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Green List (High Evidence).
Mendeliome v1.4751 MOV10L1 Zornitza Stark edited their review of gene: MOV10L1: Added comment: PMIDs 35413094 and 39122675 report five individuals from five unrelated families with biallelic MOV10L1 variants presenting with non‑obstructive azoospermia due to spermatogenic failure (maturation arrest). Immunohistochemistry, minigene splicing assays, and piRNA‑seq demonstrate loss of MOV10L1 expression and disrupted piRNA biogenesis, supporting pathogenicity.; Changed rating: GREEN; Changed publications: 39122675, 35413094; Changed phenotypes: Infertility disorder, MONDO:0005047, MOV10L1-related
Infertility and Recurrent Pregnancy Loss v1.144 Zornitza Stark Copied gene MOV10L1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.144 MOV10L1 Zornitza Stark gene: MOV10L1 was added
gene: MOV10L1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: MOV10L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOV10L1 were set to 35476666; 20534472
Phenotypes for gene: MOV10L1 were set to Spermatogenic failure 73, MIM#619878
Intellectual disability syndromic and non-syndromic v1.753 NPRL2 Lucy Spencer Classified gene: NPRL2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.753 NPRL2 Lucy Spencer Gene: nprl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.752 NPRL2 Lucy Spencer gene: NPRL2 was added
gene: NPRL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NPRL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPRL2 were set to 26505888; 34376795; 40804712; 30093711
Phenotypes for gene: NPRL2 were set to epilepsy, familial focal, with variable foci 2 (MIM#617116)
Review for gene: NPRL2 was set to AMBER
Added comment: Intellectual disability/developmental delay has been reported in some individuals with NPRL2-related epilepsy;

PMID: 30093711 3 patients with NPRL2 variants and 2 have ID, 2 also have brain abnormalities. NPRL2 forms the GATOR1 complex with DEPDC5 and NPLR3, the paper describes the phenotype of all 3 as overlapping- ID better reported in the other genes

PMID: 40804712 1 individual with mild ID and severe speech impairment. has a frameshift variant in NPRL2

PMID: 34376795 proband with seizures and dev delay/DEE, mother had ID and seizures. both had a canonical splice in NPRL2

PMID: 26505888 1 proband with ID and temporal lobe epilepsy. Had a maternally inherited missense Thr110Ser only 1 het i gnomad

Borderline amber/green for this panel
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.751 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Intellectual disability syndromic and non-syndromic v1.750 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Genetic Epilepsy v1.409 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Genetic Epilepsy v1.408 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Mendeliome v1.4751 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Mendeliome v1.4750 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Autism v0.249 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Autism v0.248 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Angelman Rett like syndromes v1.15 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Angelman Rett like syndromes v1.14 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Intellectual disability syndromic and non-syndromic v1.750 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Neurodevelopmental disorder (MONDO#0700092), PSMC5-related to Yu-Kury neurodevelopmental syndrome, MIM# 621565
Intellectual disability syndromic and non-syndromic v1.749 PSMC5 Zornitza Stark edited their review of gene: PSMC5: Changed rating: GREEN; Changed phenotypes: Yu-Kury neurodevelopmental syndrome, MIM# 621565
Mendeliome v1.4750 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Neurodevelopmental disorder (MONDO#0700092), PSMC5-related to Yu-Kury neurodevelopmental syndrome, MIM# 621565
Mendeliome v1.4749 PSMC5 Zornitza Stark reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Yu-Kury neurodevelopmental syndrome, MIM# 621565; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4749 SLIT2 Lucy Spencer changed review comment from: PMID: 26026792 reported A98T (5 hets in gnomad), S566N (111 hets in gnomad) and K904N (1 het in gnomad).

PMID: 34059960 reports another three proband with CAKUT and variants in SLIT2. D1276N (absent from gnomad), R287H (2 hets in gnomad), T757A (absent from gnomad).

6 individuals total however 1 variant is common in gnomad and another has 5 hets. No compelling functional data on the variants. The only variant with inheritance ifnromation was inherited from an unaffected parent but that was the common S566N variant.

Borderline amber/green; to: PMID: 26026792 reported A98T (5 hets in gnomad), S566N (111 hets in gnomad) and K904N (1 het in gnomad).

PMID: 34059960 reports another three proband with CAKUT and variants in SLIT2. D1276N (absent from gnomad), R287H (2 hets in gnomad), T757A (absent from gnomad).

6 individuals total however 1 variant is common in gnomad and another has 5 hets. No compelling functional data on the variants but there is a KO mouse model recapitulating the phenotype. The only variant with inheritance ifnromation was inherited from an unaffected parent but that was the common S566N variant.

Borderline amber/green
Mendeliome v1.4749 SLIT2 Lucy Spencer Phenotypes for gene: SLIT2 were changed from CAKUT MONDO:0019719, SLIT2-related to Congenital anomaly of kidney and urinary tract MONDO:0019719, SLIT2-related
Mendeliome v1.4748 SLIT2 Lucy Spencer Publications for gene: SLIT2 were set to 26026792; 15130495
Mendeliome v1.4747 SLIT2 Lucy Spencer reviewed gene: SLIT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26026792, 34059960; Phenotypes: Congenital anomaly of kidney and urinary tract MONDO:0019719, SLIT2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4747 SPRY4 Lucy Spencer changed review comment from: PMID: 31200363 identified Ser259Phe (p.236 in gnomad, only 1 het) in an individual with HH. They also had a variant in IGSF10 but it was common in gnomad. No functional data

PMID: 31781046 an individual with Kallman syndrome, identified Arg53Gln (p.30 in gnomad) which has over 80 hets and 2 homs in gnomad.

PMID: 32389901 in an individual with Kallman syndrome identified Thr68Ser (p.45 in gnomad) which only has 3 hets in gnomad. this individual also had a variant in PLXNA1 which is also amber for DSD due to high population frequencies of reported variants, and the variant in this case has 79 hets in gnomad.

PMID: 35316923 Only identified 2 common missense variants in patients with HH p.Lys177Arg and p.Ser241Tyr

So another 2 rare missense variants reported but no functional data available remains amber; to: PMID: 31200363 identified Ser259Phe (p.236 in gnomad, only 1 het) in an individual with HH. They also had a variant in IGSF10 but it was common in gnomad. No functional data

PMID: 31781046 an individual with Kallman syndrome, identified Arg53Gln (p.30 in gnomad) which has over 80 hets and 2 homs in gnomad.

PMID: 32389901 in an individual with Kallman syndrome identified Thr68Ser (p.45 in gnomad) which only has 3 hets in gnomad. this individual also had a variant in PLXNA1 which is also amber for DSD due to high population frequencies of reported variants, and the variant in this case has 79 hets in gnomad.

PMID: 35316923 Only identified 2 common missense variants in patients with HH p.Lys177Arg and p.Ser241Tyr

So another 2 rare missense variants reported but no functional data available REMAINS AMBER
Mendeliome v1.4747 SPRY4 Lucy Spencer edited their review of gene: SPRY4: Changed phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266, Neurodevelopmental disorder, MONDO:0700092, SPRY4-related
Mendeliome v1.4747 SPRY4 Lucy Spencer edited their review of gene: SPRY4: Changed rating: AMBER
Mendeliome v1.4747 SPRY4 Lucy Spencer edited their review of gene: SPRY4: Added comment: PMID: 28539120 identified Cys170Ser de novo in a proband with a neurodevelopmental condition. This individual also had 2 variants in AP4E1 (green and biallelic on the ID panel) one of which was a canonical splice. RED for this association; Changed rating: RED; Changed publications: 28539120; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SPRY4-related
Early-onset Parkinson disease v2.55 RAB32 Lucy Spencer Publications for gene: RAB32 were set to 38614108; 38858457
Early-onset Parkinson disease v2.54 RAB32 Lucy Spencer Classified gene: RAB32 as Green List (high evidence)
Early-onset Parkinson disease v2.54 RAB32 Lucy Spencer Gene: rab32 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.53 RAB32 Lucy Spencer Classified gene: RAB32 as Green List (high evidence)
Early-onset Parkinson disease v2.53 RAB32 Lucy Spencer Gene: rab32 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.52 Lucy Spencer Added reviews for gene RAB32 from panel Mendeliome
Mendeliome v1.4747 RAB32 Lucy Spencer Publications for gene: RAB32 were set to 38614108; 38858457
Mendeliome v1.4746 RAB32 Lucy Spencer Classified gene: RAB32 as Green List (high evidence)
Mendeliome v1.4746 RAB32 Lucy Spencer Gene: rab32 has been classified as Green List (High Evidence).
Mendeliome v1.4745 RAB32 Lucy Spencer reviewed gene: RAB32: Rating: GREEN; Mode of pathogenicity: None; Publications: 38858457, 38614108, 38293014, 40118982, 40568674, 41103171; Phenotypes: Parkinson disease 26, autosomal dominant, susceptibility to MIM#620923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4745 SPRY4 Lucy Spencer Publications for gene: SPRY4 were set to 23643382
Mendeliome v1.4744 SPRY4 Lucy Spencer reviewed gene: SPRY4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31200363, 31781046, 32389901, 35316923; Phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4744 WDHD1 Achchuthan Shanmugasundram gene: WDHD1 was added
gene: WDHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDHD1 were set to 41962535
Phenotypes for gene: WDHD1 were set to microcephalic osteodysplastic primordial dwarfism, MONDO:0000060
Review for gene: WDHD1 was set to GREEN
Added comment: PMID:41962535 (2026) reported the identification of biallelic hypomorphic variants in WDHD1 gene in 17 patients from 14 families with microcephalic primordial dwarfism (MPD) and a broad spectrum of additional abnormalities including acute liver failure. There is also functional evidence available from patient-derived fibroblasts which supports the disease association.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.207 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.206 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.206 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.206 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.206 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.205 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.205 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.205 JAG1 Chirag Patel Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.204 JAG1 Chirag Patel Marked gene: JAG1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.204 JAG1 Chirag Patel Gene: jag1 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.204 JAG1 Chirag Patel reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alagille syndrome, MIM#118450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.408 RYR3 Karina Sandoval reviewed gene: RYR3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39840699, 39220738, 25262651, 29667327; Phenotypes: undetermined early-onset epileptic encephalopathy (MONDO:0018614); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.39 SPPL2A Lucy Spencer Phenotypes for gene: SPPL2A were changed from Immunodeficiency 86, MIM#619549; Susceptibility to mycobacteria and Salmonella to Immunodeficiency 86, mycobacteriosis MIM#619549
Defects of intrinsic and innate immunity v1.38 SPPL2A Lucy Spencer Publications for gene: SPPL2A were set to 30127434
Defects of intrinsic and innate immunity v1.37 SPPL2A Lucy Spencer Classified gene: SPPL2A as Green List (high evidence)
Defects of intrinsic and innate immunity v1.37 SPPL2A Lucy Spencer Gene: sppl2a has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.37 Lucy Spencer Added reviews for gene SPPL2A from panel Mendeliome
Mendeliome v1.4744 SPPL2A Lucy Spencer Phenotypes for gene: SPPL2A were changed from Immunodeficiency 86, MIM#619549; Susceptibility to mycobacteria and Salmonella to Immunodeficiency 86, mycobacteriosis MIM#619549
Mendeliome v1.4743 SPPL2A Lucy Spencer Publications for gene: SPPL2A were set to 30127434
Mendeliome v1.4742 SPPL2A Lucy Spencer Classified gene: SPPL2A as Green List (high evidence)
Mendeliome v1.4742 SPPL2A Lucy Spencer Gene: sppl2a has been classified as Green List (High Evidence).
Mendeliome v1.4741 SPPL2A Lucy Spencer reviewed gene: SPPL2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30127434, 37931111, 39586751; Phenotypes: Immunodeficiency 86, mycobacteriosis MIM#619549; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.69 CRX Chirag Patel Marked gene: CRX as ready
Cone-rod Dystrophy v0.69 CRX Chirag Patel Gene: crx has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.69 Chirag Patel Added reviews for gene CRX from panel Retinitis pigmentosa
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.414 SPATA22 Lucy Spencer Phenotypes for gene: SPATA22 were changed from Premature ovarian insufficiency and nonobstructive azoospermia; Genetic infertility MONDO:0017143 to Spermatogenic failure 96, MIM#621001; Premature ovarian failure 25, MIM#621002
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.413 SPATA22 Lucy Spencer Publications for gene: SPATA22 were set to PMID: 35285020
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.412 SPATA22 Lucy Spencer Classified gene: SPATA22 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.412 SPATA22 Lucy Spencer Gene: spata22 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.143 SPATA22 Lucy Spencer Publications for gene: SPATA22 were set to 35285020
Infertility and Recurrent Pregnancy Loss v1.142 SPATA22 Lucy Spencer Classified gene: SPATA22 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.142 SPATA22 Lucy Spencer Gene: spata22 has been classified as Green List (High Evidence).
Mendeliome v1.4741 SPATA22 Lucy Spencer Publications for gene: SPATA22 were set to 35285020
Mendeliome v1.4740 SPATA22 Lucy Spencer Classified gene: SPATA22 as Green List (high evidence)
Mendeliome v1.4740 SPATA22 Lucy Spencer Gene: spata22 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.411 Lucy Spencer Added reviews for gene SPATA22 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.141 Lucy Spencer Copied gene SPATA22 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.141 SPATA22 Lucy Spencer gene: SPATA22 was added
gene: SPATA22 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,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 Spermatogenic failure 96, MIM#621001; Premature ovarian failure 25, MIM#621002
Mendeliome v1.4739 SPATA22 Lucy Spencer reviewed gene: SPATA22: Rating: GREEN; Mode of pathogenicity: None; Publications: 34392356, 35413094, 35285020; Phenotypes: Spermatogenic failure 96, MIM#621001, Premature ovarian failure 25, MIM#621002; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pierre Robin Sequence v0.64 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Intellectual disability syndromic and non-syndromic v1.749 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Mendeliome v1.4739 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Differences of Sex Development v1.50 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Differences of Sex Development v1.50 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Differences of Sex Development v1.50 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; 46,XX or XY DSD, EMX2-related
Differences of Sex Development v1.49 EMX2 Krithika Murali Classified gene: EMX2 as Green List (high evidence)
Differences of Sex Development v1.49 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Differences of Sex Development v1.48 EMX2 Krithika Murali Marked gene: EMX2 as ready
Differences of Sex Development v1.48 EMX2 Krithika Murali Gene: emx2 has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.64 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Pierre Robin sequence, EMX2-related to Pierre-Robin sequence, EMX2-related
Pierre Robin Sequence v0.64 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Pierre Robin sequence, EMX2-related
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Marked gene: EMX2 as ready
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Gene: emx2 has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Classified gene: EMX2 as Red List (low evidence)
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Gene: emx2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.115 EMX2 Krithika Murali Marked gene: EMX2 as ready
Hypogonadotropic hypogonadism v0.115 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.115 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Schizencephaly, MIM# 269160Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; 46,XX or XY DSD, EMX2-related
Hypogonadotropic hypogonadism v0.114 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Hypogonadotropic hypogonadism v0.113 EMX2 Krithika Murali Classified gene: EMX2 as Green List (high evidence)
Hypogonadotropic hypogonadism v0.113 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.749 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Intellectual disability syndromic and non-syndromic v1.748 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to complex neurodevelopmental disorder - MONDO:0100038, EMX2-related; Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; DSD, EMX2-related
Intellectual disability syndromic and non-syndromic v1.747 EMX2 Krithika Murali Classified gene: EMX2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.747 EMX2 Krithika Murali Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4739 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; DSD, EMX2-related
Pierre Robin Sequence v0.62 Krithika Murali Copied gene EMX2 from panel Mendeliome
Pierre Robin Sequence v0.62 EMX2 Krithika Murali gene: EMX2 was added
gene: EMX2 was added to Pierre Robin Sequence. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: EMX2.
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Phenotypes for gene: EMX2 were set to Schizencephaly, MIM# 269160
Mendeliome v1.4738 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Intellectual disability syndromic and non-syndromic v1.746 Krithika Murali Added reviews for gene EMX2 from panel Mendeliome
Mendeliome v1.4737 EMX2 Krithika Murali Classified gene: EMX2 as Green List (high evidence)
Mendeliome v1.4737 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.112 Krithika Murali Copied gene EMX2 from panel Mendeliome
Hypogonadotropic hypogonadism v0.112 EMX2 Krithika Murali gene: EMX2 was added
gene: EMX2 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: EMX2.
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Phenotypes for gene: EMX2 were set to Schizencephaly, MIM# 269160
Differences of Sex Development v1.48 Krithika Murali Copied gene EMX2 from panel Mendeliome
Differences of Sex Development v1.48 EMX2 Krithika Murali gene: EMX2 was added
gene: EMX2 was added to Differences of Sex Development. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: EMX2.
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Phenotypes for gene: EMX2 were set to Schizencephaly, MIM# 269160
Mendeliome v1.4736 EMX2 Krithika Murali reviewed gene: EMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41765865, 34829455, 33434492, 25577462; Phenotypes: Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related, 46,XX or XY DSD, EMX2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.361 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from Deafness, autosomal recessive 36, MIM# 609006; Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006 to Deafness, autosomal recessive 36, MIM# 609006; Deafness, autosomal dominant 91, MIM# 621556
Deafness_IsolatedAndComplex v1.360 ESPN Zornitza Stark Mode of inheritance for gene: ESPN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.359 ESPN Zornitza Stark edited their review of gene: ESPN: Changed phenotypes: Deafness, autosomal recessive 36, MIM# 609006, Deafness, autosomal dominant 91, MIM# 621556; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4736 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from Deafness, autosomal recessive 36, MIM# 609006; Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006 to Deafness, autosomal recessive 36, MIM# 609006; Deafness, autosomal dominant 91, MIM# 621556
Mendeliome v1.4735 ESPN Zornitza Stark Mode of inheritance for gene: ESPN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4734 ESPN Zornitza Stark edited their review of gene: ESPN: Changed phenotypes: Deafness, autosomal recessive 36, MIM# 609006, Deafness, autosomal dominant 91, MIM# 621556; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.68 UBAP1L Zornitza Stark Phenotypes for gene: UBAP1L were changed from Cone-rod dystrophy (MONDO:0015993), UBAP1L-related to Retinal dystrophy, Zeitz-Han type, MIM# 621558
Cone-rod Dystrophy v0.67 UBAP1L Zornitza Stark reviewed gene: UBAP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinal dystrophy, Zeitz-Han type, MIM# 621558; Mode of inheritance: None
Mendeliome v1.4734 UBAP1L Zornitza Stark Phenotypes for gene: UBAP1L were changed from Cone-rod dystrophy (MONDO:0015993), UBAP1L-related to Retinal dystrophy, Zeitz-Han type, MIM# 621558
Mendeliome v1.4733 UBAP1L Zornitza Stark reviewed gene: UBAP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinal dystrophy, Zeitz-Han type, MIM# 621558; Mode of inheritance: None
Neuromuscular Superpanel v4.429 Bryony Thompson Changed child panels to: Hereditary Neuropathy; Hereditary Spastic Paraplegia; Muscular dystrophy and myopathy_Paediatric; Limb-Girdle Muscular Dystrophy and Distal Myopathy; Motor Neurone Disease; Rhabdomyolysis and Metabolic Myopathy; Gastrointestinal neuromuscular disease; Congenital Myasthenia; Arthrogryposis; Skeletal Muscle Channelopathies
Mendeliome v1.4733 FOXJ3 Rylee Peters changed review comment from: PMID: 41803108 reports 5 individuals from 3 unrelated families with heterozygous missense FOXJ3 variants and autosomal dominant focal epilepsy with or without focal cortical dysplasia. The missense variants, p.N351S, p.I621V and p.P253T have 10 hets, 11 hets and 8 hets in gnomAD v4, respectively. Foxj3 knockdown in mouse brains results in neuronal migration defects. Functional assays demonstrate loss‑of‑function, reduced PTEN, mTOR hyper‑activation and neuronal migration defects.
Sources: Literature; to: PMID: 41803108 reports 5 individuals from 3 unrelated families with heterozygous missense FOXJ3 variants and autosomal dominant focal epilepsy with or without focal cortical dysplasia. The missense variants, p.N351S, p.I621V and p.P253T have 10 hets, 11 hets and 8 hets in gnomAD v4, respectively. Foxj3 knockdown in mouse brains results in neuronal migration defects.

Sources: Literature
Fetal anomalies v1.558 RNU4-2 Ee Ming Wong changed review comment from: Monoallelic association - PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

Biallelic association - PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature; to: PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature
Mendeliome v1.4733 FOXJ3 Rylee Peters gene: FOXJ3 was added
gene: FOXJ3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXJ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXJ3 were set to 41803108
Phenotypes for gene: FOXJ3 were set to Focal epilepsy, MONDO:0005384, FOXJ3-related
Review for gene: FOXJ3 was set to AMBER
Added comment: PMID: 41803108 reports 5 individuals from 3 unrelated families with heterozygous missense FOXJ3 variants and autosomal dominant focal epilepsy with or without focal cortical dysplasia. The missense variants, p.N351S, p.I621V and p.P253T have 10 hets, 11 hets and 8 hets in gnomAD v4, respectively. Foxj3 knockdown in mouse brains results in neuronal migration defects. Functional assays demonstrate loss‑of‑function, reduced PTEN, mTOR hyper‑activation and neuronal migration defects.
Sources: Literature
Fetal anomalies v1.558 RNU4-2 Ee Ming Wong gene: RNU4-2 was added
gene: RNU4-2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RNU4-2 were set to 38991538; 40297424; 39830270; 39423747
Phenotypes for gene: RNU4-2 were set to ReNU syndrome (MIM# 620851), AD
Mode of pathogenicity for gene: RNU4-2 was set to Other
Review for gene: RNU4-2 was set to GREEN
gene: RNU4-2 was marked as current diagnostic
Added comment: Monoallelic association - PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

Biallelic association - PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature
Defects of intrinsic and innate immunity v1.36 Sangavi Sivagnanasundram Added reviews for gene IRF9 from panel Mendeliome
Atrial Fibrillation v1.8 Sangavi Sivagnanasundram Added reviews for gene KCNA5 from panel Mendeliome
Bleeding and Platelet Disorders v1.77 Sangavi Sivagnanasundram Added reviews for gene KLKB1 from panel Mendeliome
Mendeliome v1.4732 KCNJ3 Sangavi Sivagnanasundram Deleted their review
Mendeliome v1.4732 LMAN2L Sangavi Sivagnanasundram reviewed gene: LMAN2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 40221759, 37667433; Phenotypes: intellectual disability, autosomal recessive 52, MONDO:0014815; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4732 KLKB1 Sangavi Sivagnanasundram reviewed gene: KLKB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38050365, 34847617, 33807613, 33176434, 33073460, 32202057, 31984307, 30430790; Phenotypes: inherited prekallikrein deficiency, MONDO:0012901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4732 KLF13 Sangavi Sivagnanasundram Added comment: Comment on publications: Publications weren't updated at the time of review - no new evidence has been reported.
Mendeliome v1.4732 KLF13 Sangavi Sivagnanasundram Publications for gene: KLF13 were set to
Mendeliome v1.4731 KCNJ3 Sangavi Sivagnanasundram reviewed gene: KCNJ3: Rating: AMBER; Mode of pathogenicity: None; Publications: 38597354, 37963718, 30764634; Phenotypes: Epilepsy MONDO:0005027, Hereditary spastic paraplegia MONDO:0019064, Bradycardia MONDO:0007263; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4731 KCNA5 Sangavi Sivagnanasundram reviewed gene: KCNA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 36917789, 27630060, 26129877, 34199176; Phenotypes: atrial fibrillation, familial, 7, MONDO:0012828, pulmonary arterial hypertension MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4731 HAND2 Sangavi Sivagnanasundram reviewed gene: HAND2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26676105, 26865696; Phenotypes: HAND2 related congenital heart defect MONDO:0800476; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4731 IRF9 Sangavi Sivagnanasundram reviewed gene: IRF9: Rating: AMBER; Mode of pathogenicity: None; Publications: 30143481, 30826365; Phenotypes: immunodeficiency 65, susceptibility to viral infections, MONDO:0032848; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4731 KREMEN1 Sangavi Sivagnanasundram reviewed gene: KREMEN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28813618; Phenotypes: ectodermal dysplasia 13, hair/tooth type, MONDO:0044305; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4731 LRRC23 Sangavi Sivagnanasundram reviewed gene: LRRC23: Rating: GREEN; Mode of pathogenicity: None; Publications: 39054792; Phenotypes: spermatogenic failure 92, MONDO:0970999; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4731 EMG1 Sangavi Sivagnanasundram reviewed gene: EMG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27798105, 26676230, 25708872; Phenotypes: Bowen-Conradi syndrome, MONDO:0008879; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v1.16 NDUFA5 Natalie Tan gene: NDUFA5 was added
gene: NDUFA5 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Complex I deficiency
Penetrance for gene: NDUFA5 were set to Complete
Review for gene: NDUFA5 was set to GREEN
Added comment: PMID:41916321 reports 4 individuals from 3 unrelated families with biallelic variants in NDUFA5, associated with a multi-system mitochondriopathy characterised by a complex I deficiency that was functionally confirmed via transcriptomics, proteomics and respiratory chain enzymology.
Sources: Literature
Mendeliome v1.4731 POU3F4 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: POU3F4 upstream regulatory region.
Eye Anterior Segment Abnormalities v1.21 PITX2 upstream regulatory region Sarah Milton Tag SV/CNV was removed from Region: PITX2 upstream regulatory region.
Tag regulatory region was added to Region: PITX2 upstream regulatory region.
Glaucoma congenital v1.12 PITX2 upstream regulatory region Sarah Milton Tag SV/CNV was removed from Region: PITX2 upstream regulatory region.
Tag regulatory region was added to Region: PITX2 upstream regulatory region.
Mendeliome v1.4730 PITX2 upstream regulatory region Sarah Milton Tag SV/CNV was removed from Region: PITX2 upstream regulatory region.
Tag regulatory region was added to Region: PITX2 upstream regulatory region.
Hand and foot malformations v0.89 PITX1 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: PITX1 upstream regulatory region.
Mendeliome v1.4729 PITX1 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: PITX1 upstream regulatory region.
Leukodystrophy v0.394 Sarah Milton Copied Region LMNB1 upstream region from panel Mendeliome
Leukodystrophy v0.394 LMNB1 upstream region Sarah Milton Region: LMNB1 upstream region was added
Region: LMNB1 upstream region was added to Leukodystrophy. Sources: Literature
regulatory region tags were added to Region: LMNB1 upstream region.
Mode of inheritance for Region: LMNB1 upstream region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: LMNB1 upstream region were set to PMID: 30842973; 30697589; 25701871
Phenotypes for Region: LMNB1 upstream region were set to Adult-onset autosomal dominant demyelinating leukodystrophy, MONDO:0008215
Ataxia v1.203 Sarah Milton Copied Region LMNB1 upstream region from panel Mendeliome
Ataxia v1.203 LMNB1 upstream region Sarah Milton Region: LMNB1 upstream region was added
Region: LMNB1 upstream region was added to Ataxia. Sources: Literature
regulatory region tags were added to Region: LMNB1 upstream region.
Mode of inheritance for Region: LMNB1 upstream region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: LMNB1 upstream region were set to PMID: 30842973; 30697589; 25701871
Phenotypes for Region: LMNB1 upstream region were set to Adult-onset autosomal dominant demyelinating leukodystrophy, MONDO:0008215
Regression v0.611 LMNB1 upstream region Sarah Milton Tag regulatory region was added to Region: LMNB1 upstream region.
Mendeliome v1.4728 LMNB1 upstream region Sarah Milton Tag regulatory region was added to Region: LMNB1 upstream region.
Hand and foot malformations v0.88 IHH upstream regulatory region Sarah Milton Tag regulatory region was added to Region: IHH upstream regulatory region.
Mendeliome v1.4727 IHH upstream regulatory region Sarah Milton Tag regulatory region was added to Region: IHH upstream regulatory region.
Craniosynostosis v1.85 IHH upstream regulatory region Sarah Milton Tag regulatory region was added to Region: IHH upstream regulatory region.
Pulmonary Arterial Hypertension v1.57 FOXF1 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: FOXF1 upstream regulatory region.
Mendeliome v1.4726 FOXF1 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: FOXF1 upstream regulatory region.
Fetal anomalies v1.558 DLX5 downstream regulatory region Sarah Milton GRCh38 position for DLX5 downstream regulatory region was changed from 95772554-96098424 to 96075000-96100000.
Fetal anomalies v1.557 DLX5 downstream regulatory region Sarah Milton changed review comment from: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature; to: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry encompass exons 14 to 17 of DYNC1I1, much larger deletions or disruption to the region from translocations/inversions may still be causative of disease
Sources: Literature
Hand and foot malformations v0.87 DLX5 downstream regulatory region Sarah Milton GRCh38 position for DLX5 downstream regulatory region was changed from 95772554-96098424 to 96075000-96100000.
Hand and foot malformations v0.86 DLX5 downstream regulatory region Sarah Milton changed review comment from: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature; to: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry encompass exons 14 to 17 of DYNC1I1 much larger deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature
Mendeliome v1.4725 DLX5 downstream regulatory region Sarah Milton changed review comment from: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature; to: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry encompass exons 14 to 17 of DYNC1I1 much larger deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature
Mendeliome v1.4725 DLX5 downstream regulatory region Sarah Milton GRCh38 position for DLX5 downstream regulatory region was changed from 95772554-96098424 to 96075000-96100000.
Hand and foot malformations v0.86 Sarah Milton Copied Region DLX5 downstream regulatory region from panel Mendeliome
Hand and foot malformations v0.86 DLX5 downstream regulatory region Sarah Milton Region: DLX5 downstream regulatory region was added
Region: DLX5 downstream regulatory region was added to Hand and foot malformations. Sources: Literature
regulatory region tags were added to Region: DLX5 downstream regulatory region.
Mode of inheritance for Region: DLX5 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: DLX5 downstream regulatory region were set to PMID: 26839112; 37916192; 26075025; 24459211
Phenotypes for Region: DLX5 downstream regulatory region were set to Split-hand/foot malformation 1 MIM#183600
Penetrance for Region: DLX5 downstream regulatory region were set to Incomplete
Fetal anomalies v1.557 Sarah Milton Copied Region DLX5 downstream regulatory region from panel Mendeliome
Fetal anomalies v1.557 DLX5 downstream regulatory region Sarah Milton Region: DLX5 downstream regulatory region was added
Region: DLX5 downstream regulatory region was added to Fetal anomalies. Sources: Literature
regulatory region tags were added to Region: DLX5 downstream regulatory region.
Mode of inheritance for Region: DLX5 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: DLX5 downstream regulatory region were set to PMID: 26839112; 37916192; 26075025; 24459211
Phenotypes for Region: DLX5 downstream regulatory region were set to Split-hand/foot malformation 1 MIM#183600
Penetrance for Region: DLX5 downstream regulatory region were set to Incomplete
Mendeliome v1.4724 DLX5 downstream regulatory region Sarah Milton Region: DLX5 downstream regulatory region was added
Region: DLX5 downstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: DLX5 downstream regulatory region.
Mode of inheritance for Region: DLX5 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: DLX5 downstream regulatory region were set to PMID: 26839112; 37916192; 26075025; 24459211
Phenotypes for Region: DLX5 downstream regulatory region were set to Split-hand/foot malformation 1 MIM#183600
Penetrance for Region: DLX5 downstream regulatory region were set to Incomplete
Review for Region: DLX5 downstream regulatory region was set to GREEN
Added comment: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature
Glaucoma congenital v1.11 Chirag Patel Copied gene WDR36 from panel Mendeliome
Glaucoma congenital v1.11 WDR36 Chirag Patel gene: WDR36 was added
gene: WDR36 was added to Glaucoma congenital. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: WDR36.
Mode of inheritance for gene: WDR36 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR36 were set to 15677485; 18172102; 20813748
Phenotypes for gene: WDR36 were set to Glaucoma 1, open angle, G, MIM# 609887
Monogenic Diabetes v0.224 DYRK1B Bryony Thompson Classified gene: DYRK1B as Green List (high evidence)
Monogenic Diabetes v0.224 DYRK1B Bryony Thompson Gene: dyrk1b has been classified as Green List (High Evidence).
Monogenic Diabetes v0.223 Bryony Thompson Added reviews for gene DYRK1B from panel Mendeliome
Mendeliome v1.4723 DYRK1B Bryony Thompson Classified gene: DYRK1B as Green List (high evidence)
Mendeliome v1.4723 DYRK1B Bryony Thompson Gene: dyrk1b has been classified as Green List (High Evidence).
Mendeliome v1.4722 DYRK1B Bryony Thompson reviewed gene: DYRK1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39192769, 38170957, 34786696, 34193236, 28743892; Phenotypes: abdominal obesity-metabolic syndrome 3, MONDO:0014352; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Disorders of immune dysregulation v1.43 DUOXA1 Bryony Thompson Marked gene: DUOXA1 as ready
Disorders of immune dysregulation v1.43 DUOXA1 Bryony Thompson Gene: duoxa1 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v1.43 DUOXA1 Bryony Thompson Phenotypes for gene: DUOXA1 were changed from congenital hypothyroidism MONDO:0018612 to Inborn error of immunity, MONDO:0003778
Disorders of immune dysregulation v1.42 DUOXA1 Bryony Thompson Mode of inheritance for gene: DUOXA1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v1.41 DUOXA1 Bryony Thompson edited their review of gene: DUOXA1: Changed publications: 36166305; Changed phenotypes: Inborn error of immunity, MONDO:0003778; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v1.41 Bryony Thompson Copied gene DUOXA1 from panel Mendeliome
Disorders of immune dysregulation v1.41 DUOXA1 Bryony Thompson gene: DUOXA1 was added
gene: DUOXA1 was added to Disorders of immune dysregulation. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: DUOXA1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: DUOXA1 were set to 29650690; 39988947; 36740391; 31428054
Phenotypes for gene: DUOXA1 were set to congenital hypothyroidism MONDO:0018612
Mendeliome v1.4722 DUOXA1 Bryony Thompson reviewed gene: DUOXA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36166305, 31428054, 29650690; Phenotypes: Inborn error of immunity, MONDO:0003778, congenital hypothyroidism MONDO:0018612; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.58 DROSHA Bryony Thompson Classified gene: DROSHA as Red List (low evidence)
Spontaneous coronary artery dissection v0.58 DROSHA Bryony Thompson Gene: drosha has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.57 DROSHA Bryony Thompson edited their review of gene: DROSHA: Changed rating: RED
Spontaneous coronary artery dissection v0.57 Bryony Thompson Copied gene DROSHA from panel Mendeliome
Spontaneous coronary artery dissection v0.57 DROSHA Bryony Thompson gene: DROSHA was added
gene: DROSHA was added to Spontaneous coronary artery dissection. Sources: Expert Review Amber,Literature
non-coding gene tags were added to gene: DROSHA.
Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DROSHA were set to 39654947; 35405010; 29339534
Phenotypes for gene: DROSHA were set to Neurodevelopmental disorder, MONDO:0700092; hereditary hemorrhagic telangiectasia MONDO:0019180; idiopathic spontaneous coronary artery dissection MONDO:0007385
Hereditary Haemorrhagic Telangiectasia v1.6 Bryony Thompson Copied gene DROSHA from panel Mendeliome
Hereditary Haemorrhagic Telangiectasia v1.6 DROSHA Bryony Thompson gene: DROSHA was added
gene: DROSHA was added to Hereditary Haemorrhagic Telangiectasia. Sources: Expert Review Amber,Literature
non-coding gene tags were added to gene: DROSHA.
Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DROSHA were set to 39654947; 35405010; 29339534
Phenotypes for gene: DROSHA were set to Neurodevelopmental disorder, MONDO:0700092; hereditary hemorrhagic telangiectasia MONDO:0019180; idiopathic spontaneous coronary artery dissection MONDO:0007385
Mendeliome v1.4722 DROSHA Bryony Thompson Phenotypes for gene: DROSHA were changed from Neurodevelopmental disorder (MONDO#0700092), DROSHA-related to Neurodevelopmental disorder, MONDO:0700092; hereditary hemorrhagic telangiectasia MONDO:0019180; idiopathic spontaneous coronary artery dissection MONDO:0007385
Mendeliome v1.4721 DROSHA Bryony Thompson Publications for gene: DROSHA were set to 35405010
Mendeliome v1.4720 DROSHA Bryony Thompson reviewed gene: DROSHA: Rating: AMBER; Mode of pathogenicity: None; Publications: 39654947, 35405010, 29339534; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, hereditary hemorrhagic telangiectasia MONDO:0019180, idiopathic spontaneous coronary artery dissection MONDO:0007385; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dystonia and Chorea v0.344 DRD2 Bryony Thompson Marked gene: DRD2 as ready
Dystonia and Chorea v0.344 DRD2 Bryony Thompson Gene: drd2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.344 DRD2 Bryony Thompson Classified gene: DRD2 as Green List (high evidence)
Dystonia and Chorea v0.344 DRD2 Bryony Thompson Gene: drd2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.343 DRD2 Bryony Thompson edited their review of gene: DRD2: Added comment: PMIDs 33200438, 34145635 and 38643909 report 7 individuals from 3 unrelated families with monoallelic gain‑of‑function DRD2 missense variants presenting with a hyperkinetic movement‑disorder spectrum—from adolescent‑onset chorea with cervical dystonia to infancy‑onset severe motor, cognitive and neuropsychiatric deficits. Functional assays demonstrate constitutive G‑protein activation and reduced arrestin‑β‑arrestin recruitment; two de novo cases confirm dominant inheritance. PMID 36456191 reports a mouse model of I212F with a hyperkinetic movement disorder.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed publications: 38643909, 34145635, 33974399, 33200438, 36456191
Mendeliome v1.4720 DRD2 Bryony Thompson Publications for gene: DRD2 were set to
Mendeliome v1.4719 DRD2 Bryony Thompson Classified gene: DRD2 as Green List (high evidence)
Mendeliome v1.4719 DRD2 Bryony Thompson Gene: drd2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.343 Bryony Thompson Added reviews for gene DRD2 from panel Mendeliome
Mendeliome v1.4718 DRD2 Bryony Thompson edited their review of gene: DRD2: Added comment: PMIDs 33200438, 34145635 and 38643909 report 7 individuals from 3 unrelated families with monoallelic gain‑of‑function DRD2 missense variants presenting with a hyperkinetic movement‑disorder spectrum—from adolescent‑onset chorea with cervical dystonia to infancy‑onset severe motor, cognitive and neuropsychiatric deficits. Functional assays demonstrate constitutive G‑protein activation and reduced arrestin‑β‑arrestin recruitment; two de novo cases confirm dominant inheritance.
PMID 36456191 reports a mouse model of I212F with a hyperkinetic movement disorder.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed publications: 38643909, 34145635, 33974399, 33200438, 36456191; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.410 DMRT1 Bryony Thompson Marked gene: DMRT1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.410 DMRT1 Bryony Thompson Gene: dmrt1 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.410 DMRT1 Bryony Thompson Classified gene: DMRT1 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.410 DMRT1 Bryony Thompson Gene: dmrt1 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.409 DMRT1 Bryony Thompson edited their review of gene: DMRT1: Changed rating: AMBER
Differences of Sex Development v1.47 DMRT1 Bryony Thompson edited their review of gene: DMRT1: Changed rating: AMBER
Infertility and Recurrent Pregnancy Loss v1.140 DMRT1 Bryony Thompson Publications for gene: DMRT1 were set to 26139570; 38511217; 39777458
Infertility and Recurrent Pregnancy Loss v1.139 DMRT1 Bryony Thompson Classified gene: DMRT1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.139 DMRT1 Bryony Thompson Gene: dmrt1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.409 Bryony Thompson Copied gene DMRT1 from panel Mendeliome
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.409 DMRT1 Bryony Thompson gene: DMRT1 was added
gene: DMRT1 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DMRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DMRT1 were set to 40442410; 39777458; 38511217; 36572623; 35366911; 32741963; 31745530; 31479588; 26139570; 26005864
Phenotypes for gene: DMRT1 were set to 46,XY disorder of sex development, MONDO:0020040
Infertility and Recurrent Pregnancy Loss v1.138 Bryony Thompson Added reviews for gene DMRT1 from panel Mendeliome
Differences of Sex Development v1.47 Bryony Thompson Added reviews for gene DMRT1 from panel Mendeliome
Mendeliome v1.4718 DMRT1 Bryony Thompson Publications for gene: DMRT1 were set to 31479588; 24934491; 29527098
Mendeliome v1.4717 DMRT1 Bryony Thompson Classified gene: DMRT1 as Green List (high evidence)
Mendeliome v1.4717 DMRT1 Bryony Thompson Gene: dmrt1 has been classified as Green List (High Evidence).
Mendeliome v1.4716 DMRT1 Bryony Thompson reviewed gene: DMRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40442410, 39777458, 38511217, 36572623, 35366911, 32741963, 31745530, 31479588, 26139570, 26005864; Phenotypes: 46,XX disorder of sex development, MONDO:0017576, 46,XY disorder of sex development, MONDO:0020040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypogonadotropic hypogonadism v0.111 DLG2 Bryony Thompson Marked gene: DLG2 as ready
Hypogonadotropic hypogonadism v0.111 DLG2 Bryony Thompson Gene: dlg2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.111 DLG2 Bryony Thompson Publications for gene: DLG2 were set to 37860969; 32341572
Hypogonadotropic hypogonadism v0.110 DLG2 Bryony Thompson Phenotypes for gene: DLG2 were changed from Intellectual disability (MONDO#0001071), DLG2-related; delayed puberty, self-limited, MONDO:0859205 to delayed puberty, self-limited, MONDO:0859205
Hypogonadotropic hypogonadism v0.109 Bryony Thompson Copied gene DLG2 from panel Mendeliome
Hypogonadotropic hypogonadism v0.109 DLG2 Bryony Thompson gene: DLG2 was added
gene: DLG2 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Literature
SV/CNV tags were added to gene: DLG2.
Mode of inheritance for gene: DLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLG2 were set to 37860969; 32341572
Phenotypes for gene: DLG2 were set to Intellectual disability (MONDO#0001071), DLG2-related; delayed puberty, self-limited, MONDO:0859205
Mendeliome v1.4716 DLG2 Bryony Thompson Phenotypes for gene: DLG2 were changed from Intellectual disability (MONDO#0001071), DLG2-related to Intellectual disability (MONDO#0001071), DLG2-related; delayed puberty, self-limited, MONDO:0859205
Mendeliome v1.4715 DLG2 Bryony Thompson Publications for gene: DLG2 were set to PMID: 37860969
Mendeliome v1.4714 DLG2 Bryony Thompson Classified gene: DLG2 as Green List (high evidence)
Mendeliome v1.4714 DLG2 Bryony Thompson Gene: dlg2 has been classified as Green List (High Evidence).
Mendeliome v1.4713 DLG2 Bryony Thompson reviewed gene: DLG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32341572; Phenotypes: delayed puberty, self-limited, MONDO:0859205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4713 Bryony Thompson Copied gene DIP2B from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.4713 DIP2B Bryony Thompson gene: DIP2B was added
gene: DIP2B was added to Mendeliome. Sources: Expert Review Red,Genetic Health Queensland
5'UTR tags were added to gene: DIP2B.
Mode of inheritance for gene: DIP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2B were set to 17236128; 33688487
Phenotypes for gene: DIP2B were set to Mental retardation, FRA12A type, MIM# 136630
Mode of pathogenicity for gene: DIP2B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v1.745 DIP2B Bryony Thompson Publications for gene: DIP2B were set to 17236128
Intellectual disability syndromic and non-syndromic v1.744 DIP2B Bryony Thompson Classified gene: DIP2B as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v1.744 DIP2B Bryony Thompson Added comment: Comment on list classification: STR added as an STR
Intellectual disability syndromic and non-syndromic v1.744 DIP2B Bryony Thompson Gene: dip2b has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.743 DIP2B Bryony Thompson Deleted their comment
Intellectual disability syndromic and non-syndromic v1.743 DIP2B Bryony Thompson edited their review of gene: DIP2B: Added comment: PMID 33688487 reports two siblings from one family with a heterozygous splice‑site loss‑of‑function DIP2B variant causing moderate intellectual disability.; Changed rating: RED; Changed publications: 33688487; Changed phenotypes: intellectual disability MONDO:0001071; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dyslipidaemia v0.51 CREB3L3 Bryony Thompson Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694
Dyslipidaemia v0.50 CREB3L3 Bryony Thompson Classified gene: CREB3L3 as Green List (high evidence)
Dyslipidaemia v0.50 CREB3L3 Bryony Thompson Gene: creb3l3 has been classified as Green List (High Evidence).
Dyslipidaemia v0.49 CREB3L3 Bryony Thompson edited their review of gene: CREB3L3: Added comment: Recent studies expand the evidence base for CREB3L3. PMID 34491909 adds a cohort of ten unrelated adults with heterozygous loss‑of‑function or missense CREB3L3 variants who present with severe adult‑onset hypertriglyceridemia, detailed lipoprotein profiling, and mouse‑model rescue of the lipid phenotype. PMID 41099101 reports six additional heterozygous CREB3L3 carriers among patients with multifactorial chylomicronemia syndrome.; Changed rating: GREEN; Changed publications: 32580631, 29954705, 27982131, 27291420, 26427795, 21666694, 41099101, 34491909
Dyslipidaemia v0.49 Bryony Thompson Added reviews for gene CREB3L3 from panel Mendeliome
Mendeliome v1.4712 CREB3L3 Bryony Thompson Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694
Mendeliome v1.4711 CREB3L3 Bryony Thompson Classified gene: CREB3L3 as Green List (high evidence)
Mendeliome v1.4711 CREB3L3 Bryony Thompson Gene: creb3l3 has been classified as Green List (High Evidence).
Mendeliome v1.4710 CREB3L3 Bryony Thompson edited their review of gene: CREB3L3: Added comment: Recent studies expand the evidence base for CREB3L3. PMID 34491909 adds a cohort of ten unrelated adults with heterozygous loss‑of‑function or missense CREB3L3 variants who present with severe adult‑onset hypertriglyceridemia, detailed lipoprotein profiling, and mouse‑model rescue of the lipid phenotype. PMID 41099101 reports six additional heterozygous CREB3L3 carriers among patients with multifactorial chylomicronemia syndrome.; Changed rating: GREEN; Changed publications: 41099101, 34491909, 26427795; Changed phenotypes: hypertriglyceridemia, MONDO:0005347; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Deafness_IsolatedAndComplex v1.359 COL4A6 Bryony Thompson Publications for gene: COL4A6 were set to 23714752; 33840813; 41092388
Deafness_IsolatedAndComplex v1.358 COL4A6 Bryony Thompson Classified gene: COL4A6 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.358 COL4A6 Bryony Thompson Gene: col4a6 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.357 Bryony Thompson Added reviews for gene COL4A6 from panel Mendeliome
Mendeliome v1.4710 COL4A6 Bryony Thompson Publications for gene: COL4A6 were set to 23714752; 12784310; 33840813
Mendeliome v1.4709 COL4A6 Bryony Thompson Mode of inheritance for gene: COL4A6 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.4708 COL4A6 Bryony Thompson Classified gene: COL4A6 as Green List (high evidence)
Mendeliome v1.4708 COL4A6 Bryony Thompson Gene: col4a6 has been classified as Green List (High Evidence).
Mendeliome v1.4707 COL4A6 Bryony Thompson reviewed gene: COL4A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 41092388, 40928595, 23714752, 39272213, 33840813; Phenotypes: hearing loss, X-linked 6, MONDO:0010484; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.4707 WDTC1 Zornitza Stark Marked gene: WDTC1 as ready
Mendeliome v1.4707 WDTC1 Zornitza Stark Gene: wdtc1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.408 WDTC1 Zornitza Stark Marked gene: WDTC1 as ready
Genetic Epilepsy v1.408 WDTC1 Zornitza Stark Gene: wdtc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.743 WDTC1 Zornitza Stark Marked gene: WDTC1 as ready
Intellectual disability syndromic and non-syndromic v1.743 WDTC1 Zornitza Stark Gene: wdtc1 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.66 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Dilated Cardiomyopathy v1.66 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.66 ABCC9 Zornitza Stark Classified gene: ABCC9 as Amber List (moderate evidence)
Dilated Cardiomyopathy v1.66 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v1.19 PI4KA Zornitza Stark Marked gene: PI4KA as ready
Arthrogryposis v1.19 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Arthrogryposis v1.19 PI4KA Zornitza Stark Classified gene: PI4KA as Amber List (moderate evidence)
Arthrogryposis v1.19 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Craniosynostosis v1.84 CHD3 Zornitza Stark Marked gene: CHD3 as ready
Craniosynostosis v1.84 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Craniosynostosis v1.84 CHD3 Zornitza Stark Classified gene: CHD3 as Green List (high evidence)
Craniosynostosis v1.84 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Craniosynostosis v1.83 CHD3 Zornitza Stark gene: CHD3 was added
gene: CHD3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to 37086723
Phenotypes for gene: CHD3 were set to Snijders Blok-Campeau syndrome, MIM#618205
Review for gene: CHD3 was set to GREEN
Added comment: PMID 37086723 reports three unrelated individuals with de novo heterozygous missense CHD3 variants in the helicase domain causing syndromic craniosynostosis (metopic/sagittal) with congenital onset. The variants are absent from population databases, segregation is confirmed de novo, and the paper identifies CHD3 as one of 13 genome‑wide significant craniosynostosis genes.
Sources: Literature
Craniosynostosis v1.82 KMT5B Zornitza Stark Marked gene: KMT5B as ready
Craniosynostosis v1.82 KMT5B Zornitza Stark Gene: kmt5b has been classified as Green List (High Evidence).
Craniosynostosis v1.82 KMT5B Zornitza Stark Classified gene: KMT5B as Green List (high evidence)
Craniosynostosis v1.82 KMT5B Zornitza Stark Gene: kmt5b has been classified as Green List (High Evidence).
Craniosynostosis v1.81 KMT5B Zornitza Stark edited their review of gene: KMT5B: Changed rating: GREEN
Craniosynostosis v1.81 KMT5B Zornitza Stark gene: KMT5B was added
gene: KMT5B was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: KMT5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT5B were set to 37086723
Phenotypes for gene: KMT5B were set to Intellectual developmental disorder, autosomal dominant 51 MIM# 617788
Added comment: PMID 37086723 reports 3 individuals from 3 unrelated families with heterozygous de novo loss‑of‑function (2 frameshift) or missense KMT5B variants presenting with syndromic craniosynostosis (metopic) with congenital onset. Variants are absent from population databases; de novo segregation confirmed.
Sources: Literature
Craniosynostosis v1.80 JAG1 Zornitza Stark Publications for gene: JAG1 were set to 29530693; 12244552
Craniosynostosis v1.79 JAG1 Zornitza Stark Classified gene: JAG1 as Green List (high evidence)
Craniosynostosis v1.79 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Craniosynostosis v1.78 JAG1 Zornitza Stark edited their review of gene: JAG1: Added comment: PMID 39742518 reports 6 individuals from 5 unrelated families with heterozygous loss-of-function JAG1 variants presenting with pediatric-onset craniosynostosis in the context of Alagille syndrome.; Changed rating: GREEN; Changed publications: 29530693, 12244552, 39742518; Changed phenotypes: Alagille syndrome 1, MIM# 118450
Skeletal dysplasia v0.430 AIFM1 Zornitza Stark Marked gene: AIFM1 as ready
Skeletal dysplasia v0.430 AIFM1 Zornitza Stark Gene: aifm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.430 AIFM1 Zornitza Stark Classified gene: AIFM1 as Green List (high evidence)
Skeletal dysplasia v0.430 AIFM1 Zornitza Stark Gene: aifm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.429 AIFM1 Zornitza Stark gene: AIFM1 was added
gene: AIFM1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AIFM1 were set to 33439541; 28842795; 27102849
Phenotypes for gene: AIFM1 were set to spondyloepimetaphyseal dysplasia, Bieganski type, MONDO:0010275; Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, MIM# 300232
Review for gene: AIFM1 was set to GREEN
Added comment: PMID 28842795 reports 12 affected males from 6 unrelated families with X‑linked AIFM1 variants; PMID 27102849 reports 7 affected males from 2 unrelated families with the recurrent p.Asp237Gly variant; PMID 33439541 adds 2 affected males from 2 families (one novel intronic splice variant, one previously reported synonymous variant). All cases present with short stature, kyphoscoliosis, spondylometaphyseal dysplasia, cerebral hypomyelination, motor delay and progressive neurodegeneration. Functional studies show reduced AIFM1 mRNA/protein and exon‑7 skipping, supporting loss‑of‑function. X‑linked recessive inheritance with carrier mothers (occasionally mosaic) is consistently reported.
Sources: Literature
Craniosynostosis v1.78 ADNP Zornitza Stark Marked gene: ADNP as ready
Craniosynostosis v1.78 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Craniosynostosis v1.78 ADNP Zornitza Stark Classified gene: ADNP as Green List (high evidence)
Craniosynostosis v1.78 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Craniosynostosis v1.77 ADNP Zornitza Stark gene: ADNP was added
gene: ADNP was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADNP were set to 37086723
Phenotypes for gene: ADNP were set to Helsmoortel-van der Aa syndrome MIM#615873
Review for gene: ADNP was set to GREEN
Added comment: PMID 37086723 reports 3 individuals from 3 unrelated families with heterozygous de novo loss-of-function ADNP variants presenting with syndromic craniosynostosis (sagittal or metopic) of congenital onset.
Sources: Literature
Prepair 1000+ v2.16 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly-micromelia syndrome (MIM#251230); Microcephaly, short stature, and limb abnormalities (MIM#617604) to Microcephaly-micromelia syndrome (MIM#251230); Microcephaly, short stature, and limb abnormalities (MIM#617604); Meier-Gorlin syndrome 10, MIM# 621528
Fetal anomalies v1.556 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, MONDO:0009619, Meier-Gorlin syndrome 10, MIM# 621528
Skeletal dysplasia v0.428 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230 to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; Meier-Gorlin syndrome 10, MIM# 621528
Skeletal dysplasia v0.427 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, Meier-Gorlin syndrome 10, MIM# 621528
Microcephaly v1.427 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619 to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619; Meier-Gorlin syndrome 10, MIM# 621528
Microcephaly v1.426 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, Meier-Gorlin syndrome 10, MIM# 621528
Mendeliome v1.4707 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619 to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619; Meier-Gorlin syndrome 10, MIM# 621528
Mendeliome v1.4706 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, MONDO:0009619, Meier-Gorlin syndrome 10, MIM# 621528
Skeletal Dysplasia_Fetal v0.246 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, MONDO:0009619, Meier-Gorlin syndrome 10, MIM# 621528
Mendeliome v1.4706 ASNA1 Sangavi Sivagnanasundram Tag new gene name tag was added to gene: ASNA1.
Mendeliome v1.4706 ASNA1 Sangavi Sivagnanasundram reviewed gene: ASNA1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008925; Phenotypes: cardiomyopathy, dilated, 2H MONDO:0859358; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4706 GATAD1 Sangavi Sivagnanasundram reviewed gene: GATAD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: dilated cardiomyopathy 2B MONDO:0013848; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4706 ABCC9 Sangavi Sivagnanasundram changed review comment from: LIMITED classified by ClinGen Dilated Cardiomyopathy GCEP on 04/03/2026 - https://search.clinicalgenome.org/CCID:004012

Two individuals reported with heart failure and idiopathic dilated cardiomyopathy with rare missense and frameshift variants. ClinGen also reports animal models however given the uncertainty of the GDA, gene remain as AMBER given the two reports in affected individuals.
Sources: ClinGen; to: LIMITED classified by ClinGen Dilated Cardiomyopathy GCEP on 04/03/2026 - https://search.clinicalgenome.org/CCID:004012

Two individuals reported with heart failure and idiopathic dilated cardiomyopathy with rare missense and frameshift variants. ClinGen also reports animal models however given the uncertainty of the GDA relating to DCM, gene remain as AMBER for DCM given the two reports in affected individuals.

GREEN association for Hypertrichotic osteochondrodysplasia Cantu type.

Sources: ClinGen
Mendeliome v1.4706 Sangavi Sivagnanasundram Added reviews for gene ABCC9 from panel Dilated Cardiomyopathy
Dilated Cardiomyopathy v1.65 ABCC9 Sangavi Sivagnanasundram gene: ABCC9 was added
gene: ABCC9 was added to Dilated Cardiomyopathy. Sources: ClinGen
Mode of inheritance for gene: ABCC9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABCC9 were set to 15034580
Phenotypes for gene: ABCC9 were set to dilated cardiomyopathy 1O MONDO:0012062
Review for gene: ABCC9 was set to AMBER
Added comment: LIMITED classified by ClinGen Dilated Cardiomyopathy GCEP on 04/03/2026 - https://search.clinicalgenome.org/CCID:004012

Two individuals reported with heart failure and idiopathic dilated cardiomyopathy with rare missense and frameshift variants. ClinGen also reports animal models however given the uncertainty of the GDA, gene remain as AMBER given the two reports in affected individuals.
Sources: ClinGen
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel Deleted their comment
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel commented on gene: NKX2-1: PMID 30186310 reports 2 affected individuals (father-daughter) from 1 unrelated family (heterozygous nonsense variant - c.338G>A p.Trp113*) presenting with hypogonadotropic hypogonadism and growth‑hormone deficiency. PMID 33270637 reports 1 affected individual (heterozygous missense variant - c.67G>C) with pituitary stalk interruption syndrome, choreoathetosis and hypogonadotropic hypogonadism. No segregation data for 2nd case. No functional validation for both variants.
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel Marked gene: NKX2-1 as ready
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Hypogonadotropic hypogonadism v0.107 NKX2-1 Chirag Patel Phenotypes for gene: NKX2-1 were changed from NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700 to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520
Pituitary hormone deficiency v0.208 NKX2-1 Chirag Patel Phenotypes for gene: NKX2-1 were changed from NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700 to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520
Pituitary hormone deficiency v0.207 NKX2-1 Chirag Patel Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Pituitary hormone deficiency v0.206 NKX2-1 Chirag Patel Classified gene: NKX2-1 as Red List (low evidence)
Pituitary hormone deficiency v0.206 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.205 NKX2-1 Chirag Patel edited their review of gene: NKX2-1: Added comment: PMID 30186310 reports 2 affected individuals (father-daughter) from 1 unrelated family (heterozygous nonsense variant - c.338G>A p.Trp113*) presenting with hypogonadotropic hypogonadism and growth‑hormone deficiency. PMID 33270637 reports 1 affected individual (heterozygous missense variant - c.67G>C) with pituitary stalk interruption syndrome, choreoathetosis and hypogonadotropic hypogonadism. No segregation data for 2nd case. No functional validation for both variants.; Changed rating: RED; Changed publications: 33270637, 30186310; Changed phenotypes: NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520
Pituitary hormone deficiency v0.205 NKX2-1 Chirag Patel Classified gene: NKX2-1 as Red List (low evidence)
Pituitary hormone deficiency v0.205 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.106 NKX2-1 Chirag Patel Classified gene: NKX2-1 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.106 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.105 NKX2-1 Chirag Patel Classified gene: NKX2-1 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.105 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.104 NKX2-1 Chirag Patel edited their review of gene: NKX2-1: Added comment: PMID 30186310 reports 2 affected individuals (father-daughter) from 1 unrelated family (heterozygous nonsense variant - c.338G>A p.Trp113*) presenting with hypogonadotropic hypogonadism and growth‑hormone deficiency. PMID 33270637 reports 1 affected individual (heterozygous missense variant - c.67G>C) with pituitary stalk interruption syndrome, choreoathetosis and hypogonadotropic hypogonadism. No segregation data for 2nd case. No functional validation for both variants.; Changed rating: RED; Changed publications: 33270637, 30186310; Changed phenotypes: NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520
Pituitary hormone deficiency v0.204 Chirag Patel Copied gene NKX2-1 from panel Mendeliome
Pituitary hormone deficiency v0.204 NKX2-1 Chirag Patel gene: NKX2-1 was added
gene: NKX2-1 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Royal Melbourne Hospital,Victorian Clinical Genetics Services
Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Phenotypes for gene: NKX2-1 were set to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Hypogonadotropic hypogonadism v0.104 Chirag Patel Copied gene NKX2-1 from panel Mendeliome
Hypogonadotropic hypogonadism v0.104 NKX2-1 Chirag Patel gene: NKX2-1 was added
gene: NKX2-1 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Royal Melbourne Hospital,Victorian Clinical Genetics Services
Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Phenotypes for gene: NKX2-1 were set to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Mendeliome v1.4705 Chirag Patel Added reviews for gene NKX2-1 from panel Intellectual disability syndromic and non-syndromic
Ataxia v1.202 NKX2-1 Chirag Patel Mode of inheritance for gene: NKX2-1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v1.202 NKX2-1 Chirag Patel Mode of inheritance for gene: NKX2-1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v1.202 NKX2-1 Chirag Patel Mode of inheritance for gene: NKX2-1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.556 NKX2-1 Chirag Patel Mode of inheritance for gene: NKX2-1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.203 Chirag Patel Copied gene ARHGAP5 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.203 ARHGAP5 Chirag Patel gene: ARHGAP5 was added
gene: ARHGAP5 was added to Pituitary hormone deficiency. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ARHGAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGAP5 were set to 39308770; 36178483
Phenotypes for gene: ARHGAP5 were set to Kallmann syndrome MONDO:0018800
Mendeliome v1.4704 Chirag Patel Copied gene ARHGAP5 from panel Hypogonadotropic hypogonadism
Mendeliome v1.4704 ARHGAP5 Chirag Patel gene: ARHGAP5 was added
gene: ARHGAP5 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ARHGAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGAP5 were set to 39308770; 36178483
Phenotypes for gene: ARHGAP5 were set to Kallmann syndrome MONDO:0018800
Hypogonadotropic hypogonadism v0.103 ARHGAP5 Chirag Patel Marked gene: ARHGAP5 as ready
Hypogonadotropic hypogonadism v0.103 ARHGAP5 Chirag Patel Gene: arhgap5 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.103 ARHGAP5 Chirag Patel gene: ARHGAP5 was added
gene: ARHGAP5 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: ARHGAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGAP5 were set to 39308770; 36178483
Phenotypes for gene: ARHGAP5 were set to Kallmann syndrome MONDO:0018800
Review for gene: ARHGAP5 was set to RED
Added comment: PMID 36178483 reports 2 individuals from 2 unrelated families with heterozygous truncating variants in ARHGAP5 (p.Phe790Ilefs*2, p.Tyr502Metfs*3) presenting with hypogonadotropic hypogonadism/Kallmann syndrome (childhood onset, anosmia). One variant was de novo and the other had unknown parental status. Functional zebrafish modeling showed no robust GnRH phenotype.

PMID 39308770 reported 1 patient with hypogonadotropic hypogonadism and a heterozygous ARHGAP5 variant (p.Val269Leu - classified as VUS) but provided no detailed phenotype, segregation or functional data.
Sources: Literature
Pituitary hormone deficiency v0.202 AMH Chirag Patel Marked gene: AMH as ready
Pituitary hormone deficiency v0.202 AMH Chirag Patel Gene: amh has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.202 Chirag Patel Copied gene AMH from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.202 AMH Chirag Patel gene: AMH was added
gene: AMH was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: AMH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AMH were set to 31291191
Phenotypes for gene: AMH were set to Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.4703 AMH Chirag Patel Mode of inheritance for gene: AMH was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4702 AMH Chirag Patel Phenotypes for gene: AMH were changed from Persistent Mullerian duct syndrome, type I (MIM#261550) to Persistent Mullerian duct syndrome, type I (MIM#261550); Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.4701 AMH Chirag Patel Publications for gene: AMH were set to 32172781; 31291191
Mendeliome v1.4701 AMH Chirag Patel Publications for gene: AMH were set to 32172781
Mendeliome v1.4700 AMH Chirag Patel Mode of inheritance for gene: AMH was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4699 Chirag Patel Added reviews for gene AMH from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.102 AMH Chirag Patel Classified gene: AMH as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v0.102 AMH Chirag Patel Gene: amh has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.101 AMH Chirag Patel Marked gene: AMH as ready
Hypogonadotropic hypogonadism v0.101 AMH Chirag Patel Gene: amh has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.101 AMH Chirag Patel gene: AMH was added
gene: AMH was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: AMH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AMH were set to 31291191
Phenotypes for gene: AMH were set to Hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: AMH was set to AMBER
Added comment: PMID 31291191 reports 3 individuals from 3 unrelated families with heterozygous missense variants in AMH gene (p.Thr99Ser, p.Pro151Ser, p.Asp238Glu). They presented with childhood‑onset hypogonadotropic hypogonadism (CHH) often with variable anosmia (Kallmann syndrome). Two variants were inherited from an affected parent, and 1 variant had unknown parental status. Functional studies demonstrated significantly reduced AMH secretion in transfected COS-7 cells, impaired GnRH‑neuron migration, and decreased GnRH release. AMH is expressed in migratory GnRH neurons in both mouse and human fetuses.
Sources: Literature
Pituitary hormone deficiency v0.201 SOX11 Chirag Patel Marked gene: SOX11 as ready
Pituitary hormone deficiency v0.201 SOX11 Chirag Patel Gene: sox11 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.201 Chirag Patel Copied gene SOX11 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.201 SOX11 Chirag Patel gene: SOX11 was added
gene: SOX11 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert Review,Expert Review
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29459093; 24886874; 33086258; 33785884; 35642566; 35341651
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Mendeliome v1.4698 ACTL6A Sangavi Sivagnanasundram reviewed gene: ACTL6A: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004045; Phenotypes: ACTL6A-related BAFopathy MONDO:0700121; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.200 Chirag Patel Added reviews for gene NDNF from panel Hypogonadotropic hypogonadism
Mendeliome v1.4698 Chirag Patel Added reviews for gene NDNF from panel Hypogonadotropic hypogonadism
Differences of Sex Development v1.46 Chirag Patel Added reviews for gene NDNF from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.100 NDNF Chirag Patel reviewed gene: NDNF: Rating: AMBER; Mode of pathogenicity: None; Publications: 36245975; Phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v0.120 IYD Chirag Patel Phenotypes for gene: IYD were changed from Thyroid dyshormonogenesis 4, MIM# 274800 to Thyroid dyshormonogenesis 4, MIM# 274800
Congenital hypothyroidism v0.119 IYD Chirag Patel Phenotypes for gene: IYD were changed from childhood/adolescent onset hypothyroidism; Thyroid dyshormonogenesis 4, 274800; normal iodide organification; Congenital hypothyroidism; raised urinary MIT and DIT; goitre to Thyroid dyshormonogenesis 4, MIM# 274800
Congenital hypothyroidism v0.118 IYD Chirag Patel Mode of inheritance for gene: IYD was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4697 Chirag Patel Added reviews for gene IYD from panel Congenital hypothyroidism
Congenital hypothyroidism v0.117 IYD Chirag Patel Marked gene: IYD as ready
Congenital hypothyroidism v0.117 IYD Chirag Patel Gene: iyd has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.117 IYD Chirag Patel reviewed gene: IYD: Rating: GREEN; Mode of pathogenicity: None; Publications: 39106437, 36633921; Phenotypes: Thyroid dyshormonogenesis 4, MIM# 274800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.555 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Fetal anomalies v1.554 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.743 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Intellectual disability syndromic and non-syndromic v1.742 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.593 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Callosome v0.592 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.408 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Genetic Epilepsy v1.407 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.122 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Muscular dystrophy and myopathy_Paediatric v1.121 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.426 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Microcephaly v1.425 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4696 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Mendeliome v1.4695 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v1.100 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Cerebellar and Pontocerebellar Hypoplasia v1.99 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4695 CADM3 Sangavi Sivagnanasundram reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:009251; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2FF MONDO:0030433; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4695 KCNJ4 Chirag Patel changed review comment from: PMID 41830586 reports 4 individuals from 4 families with heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature; to: PMID 41830586 reports 4 individuals from 4 families with rare heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature
Genetic Epilepsy v1.407 KCNJ4 Chirag Patel changed review comment from: PMID 41830586 reports 4 individuals from 4 families with heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature; to: PMID 41830586 reports 4 individuals from 4 families with rare heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.742 KCNJ4 Chirag Patel changed review comment from: PMID 41830586 reports 4 individuals from 4 families with heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature; to: PMID 41830586 reports 4 individuals from 4 families with rare heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.742 KCNJ4 Chirag Patel Marked gene: KCNJ4 as ready
Intellectual disability syndromic and non-syndromic v1.742 KCNJ4 Chirag Patel Gene: kcnj4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.407 KCNJ4 Chirag Patel Marked gene: KCNJ4 as ready
Genetic Epilepsy v1.407 KCNJ4 Chirag Patel Gene: kcnj4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.742 Chirag Patel Copied gene KCNJ4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.742 KCNJ4 Chirag Patel gene: KCNJ4 was added
gene: KCNJ4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: KCNJ4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ4 were set to 41830586
Phenotypes for gene: KCNJ4 were set to Neurodevelopmental disorder, MONDO:0700092, KCNJ4-related
Mode of pathogenicity for gene: KCNJ4 was set to Other
Genetic Epilepsy v1.407 Chirag Patel Copied gene KCNJ4 from panel Mendeliome
Genetic Epilepsy v1.407 KCNJ4 Chirag Patel gene: KCNJ4 was added
gene: KCNJ4 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: KCNJ4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ4 were set to 41830586
Phenotypes for gene: KCNJ4 were set to Neurodevelopmental disorder, MONDO:0700092, KCNJ4-related
Mode of pathogenicity for gene: KCNJ4 was set to Other
Mendeliome v1.4695 KCNJ4 Chirag Patel Marked gene: KCNJ4 as ready
Mendeliome v1.4695 KCNJ4 Chirag Patel Gene: kcnj4 has been classified as Green List (High Evidence).
Mendeliome v1.4695 KCNJ4 Chirag Patel Classified gene: KCNJ4 as Green List (high evidence)
Mendeliome v1.4695 KCNJ4 Chirag Patel Gene: kcnj4 has been classified as Green List (High Evidence).
Mendeliome v1.4694 KCNJ4 Chirag Patel gene: KCNJ4 was added
gene: KCNJ4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNJ4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ4 were set to 41830586
Phenotypes for gene: KCNJ4 were set to Neurodevelopmental disorder, MONDO:0700092, KCNJ4-related
Mode of pathogenicity for gene: KCNJ4 was set to Other
Review for gene: KCNJ4 was set to GREEN
Added comment: PMID 41830586 reports 4 individuals from 4 families with heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature
Congenital Disorders of Glycosylation v1.85 Sarah Milton Added reviews for gene PIGM from panel Mendeliome
Overgrowth v1.21 Lucy Spencer Added reviews for gene SPIN4 from panel Mendeliome
Mendeliome v1.4693 SPIN4 Lucy Spencer reviewed gene: SPIN4: Rating: AMBER; Mode of pathogenicity: None; Publications: Lui-Jee-Baron syndrome MIM#301114; Phenotypes: 41780720, 41158422; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v1.741 Lucy Spencer Copied gene WDTC1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.741 WDTC1 Lucy Spencer gene: WDTC1 was added
gene: WDTC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: WDTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDTC1 were set to 41793087
Phenotypes for gene: WDTC1 were set to Neurodevelopmental disorder MONDO:0700092, WDTC1-related
Genetic Epilepsy v1.406 Lucy Spencer Copied gene WDTC1 from panel Mendeliome
Genetic Epilepsy v1.406 WDTC1 Lucy Spencer gene: WDTC1 was added
gene: WDTC1 was added to Genetic Epilepsy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: WDTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDTC1 were set to 41793087
Phenotypes for gene: WDTC1 were set to Neurodevelopmental disorder MONDO:0700092, WDTC1-related
Mendeliome v1.4693 WDTC1 Lucy Spencer Classified gene: WDTC1 as Amber List (moderate evidence)
Mendeliome v1.4693 WDTC1 Lucy Spencer Gene: wdtc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4692 WDTC1 Lucy Spencer gene: WDTC1 was added
gene: WDTC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDTC1 were set to 41793087
Phenotypes for gene: WDTC1 were set to Neurodevelopmental disorder MONDO:0700092, WDTC1-related
Review for gene: WDTC1 was set to AMBER
Added comment: PMID 41793087 reports 7 individuals from 6 unrelated families with heterozygous variants in WDTC1. 1 from the DDD study. 3 missense, 2 PTCs, 1 canonical splice. 2 missense and 1 PTC were de novo, no inheritance info for the splice. The other PTC was inherited from an affected mother (mild ID and seizures), and the other missense was paternally inherited from an unaffected father- this variant Arg675Gln also has 15 hets in gnomad. The other 2 missense are also present in gnomad with 2 and 7 hets, while the PTC and splice variants are absent or only have 1 het (PTCS in general are also rare in gnomad in this gene).

The features in these probands were quite general- developmental delay, intellectual disability, seizures and variable additional features such as autism, ADHD and facial dysmorphism. No experimental functional validation was provided.

Only counting the PTCs and splice due to the gnomad counts for the missense we have 4 patients from 3 families, only 1 de novo, 1 inherited from a mildly affected mother and all with a very general phenotype with no experimental evidence. Keeping as amber for the moment
Sources: Literature
Monogenic Diabetes v0.222 APPL1 Sangavi Sivagnanasundram Tag refuted tag was added to gene: APPL1.
Monogenic Diabetes v0.222 Sangavi Sivagnanasundram Added reviews for gene APPL1 from panel Mendeliome
Mendeliome v1.4691 APPL1 Sangavi Sivagnanasundram Tag refuted tag was added to gene: APPL1.
Mendeliome v1.4691 APPL1 Sangavi Sivagnanasundram reviewed gene: APPL1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004159; Phenotypes: monogenic diabetes MONDO:0015967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4691 NME8 Sangavi Sivagnanasundram Phenotypes for gene: NME8 were changed from Ciliary dyskinesia, primary, 6, MIM# 610852 to Ciliary dyskinesia, primary, 6, MIM# 610852; primary ciliary dyskinesia MONDO:0016575
Mendeliome v1.4690 NME8 Sangavi Sivagnanasundram Added comment: Comment on phenotypes: primary ciliary dyskinesia MONDO:0016575
Mendeliome v1.4690 NME8 Sangavi Sivagnanasundram Phenotypes for gene: NME8 were changed from Ciliary dyskinesia, primary, 6, MIM# 610852 to Ciliary dyskinesia, primary, 6, MIM# 610852
Mendeliome v1.4689 NME8 Sangavi Sivagnanasundram Tag disputed tag was added to gene: NME8.
Mendeliome v1.4689 NME8 Sangavi Sivagnanasundram reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005652; Phenotypes: primary ciliary dyskinesia MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4689 PIGM Sarah Milton reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: 41782195, 39912323, 39425582, 39119839, 31445883; Phenotypes: hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency, MONDO:0012465; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.64 SLC6A6 Lucy Spencer edited their review of gene: SLC6A6: Changed rating: AMBER
Dilated Cardiomyopathy v1.64 SLC6A6 Lucy Spencer changed review comment from: This gene was reviewed as limited by ClinGen in 2023 however PMID: 41343195 had not yet been published at that time

PMID: 41343195 four families with Leber congenital amaurosis or early-onset retinal dystrophy, all have homozygous variants in SLC6A6- 2 missense, 1 in frame del, 1 nonsense. Thr249Ile, Ala294Thr, Phe404_Glu449del, Trp113Ter. in 1 family the variant segregated with disease as homozygous in 4 affected siblings and heterozygous in unaffected siblings. Some functional evidence available for the 2 missense demonstrating LOF effects. No clear cardiac phenotype was observed in these families.

PMIDs: 31345061, 31903486 reported Ala78Glu and Gly399Val homozygous; to: This gene was reviewed as limited by ClinGen in 2023 however PMID: 41343195 had not yet been published at that time

PMID: 41343195 four families with Leber congenital amaurosis or early-onset retinal dystrophy, all have homozygous variants in SLC6A6- 2 missense, 1 in frame del, 1 nonsense. Thr249Ile, Ala294Thr, Phe404_Glu449del, Trp113Ter. in 1 family the variant segregated with disease as homozygous in 4 affected siblings and heterozygous in unaffected siblings. Some functional evidence available for the 2 missense demonstrating LOF effects. No clear cardiac phenotype was observed in these families- still amber for the cardiac association

PMIDs: 31345061, 31903486 reported Ala78Glu and Gly399Val homozygous
Dilated Cardiomyopathy v1.64 Lucy Spencer Added reviews for gene SLC6A6 from panel Mendeliome
Aminoacidopathy v1.143 SLC6A6 Lucy Spencer Phenotypes for gene: SLC6A6 were changed from hypotaurinemic retinal degeneration and cardiomyopathy MONDO:0007777 to Hypotaurinemic retinal degeneration and cardiomyopathy MMI#145350
Aminoacidopathy v1.142 SLC6A6 Lucy Spencer Publications for gene: SLC6A6 were set to 31903486; 31345061
Aminoacidopathy v1.141 SLC6A6 Lucy Spencer Classified gene: SLC6A6 as Green List (high evidence)
Aminoacidopathy v1.141 SLC6A6 Lucy Spencer Gene: slc6a6 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.67 SLC6A6 Lucy Spencer Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034
Cone-rod Dystrophy v0.66 SLC6A6 Lucy Spencer Phenotypes for gene: SLC6A6 were changed from Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Cone-rod retinopathy; cardiomyopathy to Hypotaurinemic retinal degeneration and cardiomyopathy MMI#145350
Cone-rod Dystrophy v0.65 SLC6A6 Lucy Spencer Classified gene: SLC6A6 as Green List (high evidence)
Cone-rod Dystrophy v0.65 SLC6A6 Lucy Spencer Gene: slc6a6 has been classified as Green List (High Evidence).
Mendeliome v1.4689 SLC6A6 Lucy Spencer Phenotypes for gene: SLC6A6 were changed from Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Early retinal degeneration; cardiomyopathy to Hypotaurinaemic retinal degeneration and cardiomyopathy MIM#145350
Mendeliome v1.4688 SLC6A6 Lucy Spencer Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034
Mendeliome v1.4687 SLC6A6 Lucy Spencer Classified gene: SLC6A6 as Green List (high evidence)
Mendeliome v1.4687 SLC6A6 Lucy Spencer Gene: slc6a6 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.64 Lucy Spencer Added reviews for gene SLC6A6 from panel Mendeliome
Aminoacidopathy v1.140 Lucy Spencer Added reviews for gene SLC6A6 from panel Mendeliome
Mendeliome v1.4686 SLC6A6 Lucy Spencer reviewed gene: SLC6A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 41343195; Phenotypes: Hypotaurinemic retinal degeneration and cardiomyopathy MMI#145350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.740 SLC6A17 Lucy Spencer Publications for gene: SLC6A17 were set to 25704603; 23672601
Intellectual disability syndromic and non-syndromic v1.739 SLC6A17 Lucy Spencer Classified gene: SLC6A17 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.739 SLC6A17 Lucy Spencer Gene: slc6a17 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.738 Lucy Spencer Added reviews for gene SLC6A17 from panel Mendeliome
Growth failure v1.102 Lucy Spencer Copied gene SLC6A17 from panel Mendeliome
Growth failure v1.102 SLC6A17 Lucy Spencer gene: SLC6A17 was added
gene: SLC6A17 was added to Growth failure. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC6A17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A17 were set to 25704603; 23672601; 40897375
Phenotypes for gene: SLC6A17 were set to Intellectual developmental disorder, autosomal recessive 48, MIM# 616269
Mendeliome v1.4686 SLC6A17 Lucy Spencer Publications for gene: SLC6A17 were set to 25704603; 23672601
Mendeliome v1.4685 SLC6A17 Lucy Spencer Classified gene: SLC6A17 as Green List (high evidence)
Mendeliome v1.4685 SLC6A17 Lucy Spencer Gene: slc6a17 has been classified as Green List (High Evidence).
Mendeliome v1.4684 SLC6A17 Lucy Spencer reviewed gene: SLC6A17: Rating: GREEN; Mode of pathogenicity: None; Publications: 25704603, 40897375; Phenotypes: Intellectual developmental disorder, autosomal recessive 48 MIM#616269; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.737 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from pontocerebellar hypoplasia type 2A MONDO:0010190 to Pontocerebellar hypoplasia type 2A 277470; Pontocerebellar hypoplasia type 4 225753
Intellectual disability syndromic and non-syndromic v1.736 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to 20301773
Intellectual disability syndromic and non-syndromic v1.735 TSEN54 Zornitza Stark Deleted their comment
Intellectual disability syndromic and non-syndromic v1.735 Zornitza Stark Added reviews for gene TSEN54 from panel Mendeliome
Mendeliome v1.4684 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from Pontocerebellar hypoplasia type 2A 277470; Pontocerebellar hypoplasia type 4 225753; Ataxia to Pontocerebellar hypoplasia type 2A 277470; Pontocerebellar hypoplasia type 4 225753
Mendeliome v1.4683 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to 24938831
Mendeliome v1.4682 TSEN54 Zornitza Stark edited their review of gene: TSEN54: Added comment: Reports from PMID 32697043, PMID 35962274, PMID 41825724, PMID 32214227, PMID 39400946, PMID 39634246, PMID 38347586, PMID 39034883, PMID 29410950, PMID 27570394, and PMID 34085948 add a total of 30 patients from 28 unrelated families with autosomal recessive TSEN54 variants (predominantly the founder missense c.919G>T) causing pontocerebellar hypoplasia with microcephaly, severe developmental delay, seizures and characteristic cerebellar‑pontine hypoplasia. PMID 39034883 provides functional validation using patient‑derived iPSC organoids that recapitulate the neuroanatomical phenotype.

MOI changed to biallelic as evidence for mono allelic association is very limited.; Changed publications: 41825724, 39634246, 39400946, 39034883, 38622473, 38347586, 35962274, 34085948, 32697043, 32214227, 29410950, 27570394, 27430971; Changed phenotypes: Pontocerebellar hypoplasia type 2A 277470, Pontocerebellar hypoplasia type 4 225753
Syndromic Retinopathy v0.256 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Syndromic Retinopathy v0.256 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.46 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Rhabdomyolysis and Metabolic Myopathy v1.46 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.190 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Hereditary Neuropathy v1.190 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Ataxia v1.201 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Ataxia v1.201 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.356 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Deafness_IsolatedAndComplex v1.356 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Genetic Epilepsy v1.405 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Genetic Epilepsy v1.405 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Mitochondrial disease v1.16 MT-TY Zornitza Stark Tag somatic was removed from gene: MT-TY.
Syndromic Retinopathy v0.256 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Syndromic Retinopathy v0.256 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Rhabdomyolysis and Metabolic Myopathy v1.46 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Rhabdomyolysis and Metabolic Myopathy v1.46 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Hereditary Neuropathy v1.190 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Hereditary Neuropathy v1.190 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Genetic Epilepsy v1.405 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Genetic Epilepsy v1.405 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Deafness_IsolatedAndComplex v1.356 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Deafness_IsolatedAndComplex v1.356 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Ataxia v1.201 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Ataxia v1.201 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Ataxia. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Cardiomyopathy_Paediatric v0.229 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Cardiomyopathy_Paediatric v0.229 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.255 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Syndromic Retinopathy v0.255 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Monogenic Diabetes v0.221 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Monogenic Diabetes v0.221 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.189 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Hereditary Neuropathy v1.189 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Dystonia and Chorea v0.342 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Dystonia and Chorea v0.342 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Ataxia v1.200 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Ataxia v1.200 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.734 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Intellectual disability syndromic and non-syndromic v1.734 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.355 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Deafness_IsolatedAndComplex v1.355 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Regression v0.610 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Regression v0.610 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Genetic Epilepsy v1.404 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Genetic Epilepsy v1.404 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Optic Atrophy v1.72 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Optic Atrophy v1.72 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Microcephaly v1.425 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Microcephaly v1.425 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.255 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Syndromic Retinopathy v0.255 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Regression v0.610 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Regression v0.610 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Regression. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Optic Atrophy v1.72 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Optic Atrophy v1.72 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Optic Atrophy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Monogenic Diabetes v0.221 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Monogenic Diabetes v0.221 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Monogenic Diabetes. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Microcephaly v1.425 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Microcephaly v1.425 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Microcephaly. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Intellectual disability syndromic and non-syndromic v1.734 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.734 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Hereditary Neuropathy v1.189 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Hereditary Neuropathy v1.189 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Genetic Epilepsy v1.404 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Genetic Epilepsy v1.404 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Dystonia and Chorea v0.342 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Dystonia and Chorea v0.342 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Dystonia and Chorea. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Deafness_IsolatedAndComplex v1.355 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.355 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Cardiomyopathy_Paediatric v0.229 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.229 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Ataxia v1.200 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Ataxia v1.200 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Ataxia. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Cardiomyopathy_Paediatric v0.228 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Cardiomyopathy_Paediatric v0.228 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Monogenic Diabetes v0.220 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Monogenic Diabetes v0.220 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.45 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Rhabdomyolysis and Metabolic Myopathy v1.45 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.188 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Hereditary Neuropathy v1.188 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Dystonia and Chorea v0.341 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Dystonia and Chorea v0.341 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Ataxia v1.199 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Ataxia v1.199 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.733 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Intellectual disability syndromic and non-syndromic v1.733 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.354 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Deafness_IsolatedAndComplex v1.354 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Regression v0.609 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Regression v0.609 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Genetic Epilepsy v1.403 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Genetic Epilepsy v1.403 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Cataract v1.3 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Cataract v1.3 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.45 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.45 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Regression v0.609 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Regression v0.609 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Regression. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Monogenic Diabetes v0.220 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Monogenic Diabetes v0.220 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Monogenic Diabetes. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Intellectual disability syndromic and non-syndromic v1.733 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.733 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Hereditary Neuropathy v1.188 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Hereditary Neuropathy v1.188 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Genetic Epilepsy v1.403 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Genetic Epilepsy v1.403 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Dystonia and Chorea v0.341 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Dystonia and Chorea v0.341 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Dystonia and Chorea. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Deafness_IsolatedAndComplex v1.354 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.354 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Cataract v1.3 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Cataract v1.3 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Cataract. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Cardiomyopathy_Paediatric v0.228 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.228 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Ataxia v1.199 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Ataxia v1.199 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Ataxia. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Syndromic Retinopathy v0.254 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Syndromic Retinopathy v0.254 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Monogenic Diabetes v0.219 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Monogenic Diabetes v0.219 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.44 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Rhabdomyolysis and Metabolic Myopathy v1.44 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.353 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Deafness_IsolatedAndComplex v1.353 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Genetic Epilepsy v1.402 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Genetic Epilepsy v1.402 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Optic Atrophy v1.71 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Optic Atrophy v1.71 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.254 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Syndromic Retinopathy v0.254 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Rhabdomyolysis and Metabolic Myopathy v1.44 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.44 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Optic Atrophy v1.71 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Optic Atrophy v1.71 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Optic Atrophy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Monogenic Diabetes v0.219 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Monogenic Diabetes v0.219 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Monogenic Diabetes. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Genetic Epilepsy v1.402 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Genetic Epilepsy v1.402 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Deafness_IsolatedAndComplex v1.353 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.353 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Hypogonadotropic hypogonadism v0.100 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Hypogonadotropic hypogonadism v0.100 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.227 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Cardiomyopathy_Paediatric v0.227 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.253 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Syndromic Retinopathy v0.253 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.218 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Monogenic Diabetes v0.218 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Ataxia v1.198 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Ataxia v1.198 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.732 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Intellectual disability syndromic and non-syndromic v1.732 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.352 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Deafness_IsolatedAndComplex v1.352 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.401 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Genetic Epilepsy v1.401 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Cataract v1.2 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Cataract v1.2 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.253 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Syndromic Retinopathy v0.253 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Monogenic Diabetes v0.218 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Monogenic Diabetes v0.218 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Monogenic Diabetes. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Intellectual disability syndromic and non-syndromic v1.732 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.732 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Hypogonadotropic hypogonadism v0.100 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Hypogonadotropic hypogonadism v0.100 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Genetic Epilepsy v1.401 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Genetic Epilepsy v1.401 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Deafness_IsolatedAndComplex v1.352 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.352 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Cataract v1.2 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Cataract v1.2 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Cataract. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Cardiomyopathy_Paediatric v0.227 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.227 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Ataxia v1.198 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Ataxia v1.198 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Ataxia. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Stroke v1.48 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Stroke v1.48 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.43 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Rhabdomyolysis and Metabolic Myopathy v1.43 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.731 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Intellectual disability syndromic and non-syndromic v1.731 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.351 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Deafness_IsolatedAndComplex v1.351 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.400 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Genetic Epilepsy v1.400 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Stroke v1.48 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Stroke v1.48 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Stroke. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Rhabdomyolysis and Metabolic Myopathy v1.43 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.43 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Intellectual disability syndromic and non-syndromic v1.731 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.731 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Genetic Epilepsy v1.400 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Genetic Epilepsy v1.400 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Deafness_IsolatedAndComplex v1.351 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.351 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Intellectual disability syndromic and non-syndromic v1.730 MT-TR Zornitza Stark Marked gene: MT-TR as ready
Intellectual disability syndromic and non-syndromic v1.730 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Genetic Epilepsy v1.399 MT-TR Zornitza Stark Marked gene: MT-TR as ready
Genetic Epilepsy v1.399 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Optic Atrophy v1.70 MT-TR Zornitza Stark Marked gene: MT-TR as ready
Optic Atrophy v1.70 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.252 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Syndromic Retinopathy v0.252 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Rhabdomyolysis and Metabolic Myopathy v1.42 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.42 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Optic Atrophy v1.70 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Optic Atrophy v1.70 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Optic Atrophy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Intellectual disability syndromic and non-syndromic v1.730 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.730 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Genetic Epilepsy v1.399 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Genetic Epilepsy v1.399 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Cardiomyopathy_Paediatric v0.226 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.226 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Stroke v1.47 MT-TQ Zornitza Stark Marked gene: MT-TQ as ready
Stroke v1.47 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.41 MT-TQ Zornitza Stark Marked gene: MT-TQ as ready
Rhabdomyolysis and Metabolic Myopathy v1.41 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.69 MT-TQ Zornitza Stark Marked gene: MT-TQ as ready
Optic Atrophy v1.69 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Stroke v1.47 Zornitza Stark Copied gene MT-TQ from panel Mitochondrial disease
Stroke v1.47 MT-TQ Zornitza Stark gene: MT-TQ was added
gene: MT-TQ was added to Stroke. Sources: Expert Review Amber,Expert list
mtDNA tags were added to gene: MT-TQ.
Mode of inheritance for gene gene: MT-TQ was set to MITOCHONDRIAL
Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Phenotypes for gene: MT-TQ were set to Mitochondrial disease (MONDO:0044970), MT-TQ-related
Rhabdomyolysis and Metabolic Myopathy v1.41 Zornitza Stark Copied gene MT-TQ from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.41 MT-TQ Zornitza Stark gene: MT-TQ was added
gene: MT-TQ was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Amber,Expert list
mtDNA tags were added to gene: MT-TQ.
Mode of inheritance for gene gene: MT-TQ was set to MITOCHONDRIAL
Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Phenotypes for gene: MT-TQ were set to Mitochondrial disease (MONDO:0044970), MT-TQ-related
Optic Atrophy v1.69 Zornitza Stark Copied gene MT-TQ from panel Mitochondrial disease
Optic Atrophy v1.69 MT-TQ Zornitza Stark gene: MT-TQ was added
gene: MT-TQ was added to Optic Atrophy. Sources: Expert Review Amber,Expert list
mtDNA tags were added to gene: MT-TQ.
Mode of inheritance for gene gene: MT-TQ was set to MITOCHONDRIAL
Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Phenotypes for gene: MT-TQ were set to Mitochondrial disease (MONDO:0044970), MT-TQ-related
Rhabdomyolysis and Metabolic Myopathy v1.40 MT-TL2 Zornitza Stark Marked gene: MT-TL2 as ready
Rhabdomyolysis and Metabolic Myopathy v1.40 MT-TL2 Zornitza Stark Gene: mt-tl2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.187 MT-TL2 Zornitza Stark Marked gene: MT-TL2 as ready
Hereditary Neuropathy v1.187 MT-TL2 Zornitza Stark Gene: mt-tl2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.350 MT-TL2 Zornitza Stark Marked gene: MT-TL2 as ready
Deafness_IsolatedAndComplex v1.350 MT-TL2 Zornitza Stark Gene: mt-tl2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.40 Zornitza Stark Copied gene MT-TL2 from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.40 MT-TL2 Zornitza Stark gene: MT-TL2 was added
gene: MT-TL2 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TL2.
Mode of inheritance for gene gene: MT-TL2 was set to MITOCHONDRIAL
Publications for gene: MT-TL2 were set to 8923013; 12398839; 19718780; 18977334; 21819490; 15649400; 15591266; 23847141; 20022607; 29052516
Phenotypes for gene: MT-TL2 were set to Mitochondrial disease (MONDO:0044970), MT-TL2-related
Hereditary Neuropathy v1.187 Zornitza Stark Copied gene MT-TL2 from panel Mitochondrial disease
Hereditary Neuropathy v1.187 MT-TL2 Zornitza Stark gene: MT-TL2 was added
gene: MT-TL2 was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TL2.
Mode of inheritance for gene gene: MT-TL2 was set to MITOCHONDRIAL
Publications for gene: MT-TL2 were set to 8923013; 12398839; 19718780; 18977334; 21819490; 15649400; 15591266; 23847141; 20022607; 29052516
Phenotypes for gene: MT-TL2 were set to Mitochondrial disease (MONDO:0044970), MT-TL2-related
Deafness_IsolatedAndComplex v1.350 Zornitza Stark Copied gene MT-TL2 from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.350 MT-TL2 Zornitza Stark gene: MT-TL2 was added
gene: MT-TL2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TL2.
Mode of inheritance for gene gene: MT-TL2 was set to MITOCHONDRIAL
Publications for gene: MT-TL2 were set to 8923013; 12398839; 19718780; 18977334; 21819490; 15649400; 15591266; 23847141; 20022607; 29052516
Phenotypes for gene: MT-TL2 were set to Mitochondrial disease (MONDO:0044970), MT-TL2-related
Rhabdomyolysis and Metabolic Myopathy v1.39 MT-TM Zornitza Stark Marked gene: MT-TM as ready
Rhabdomyolysis and Metabolic Myopathy v1.39 MT-TM Zornitza Stark Gene: mt-tm has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.39 Zornitza Stark Copied gene MT-TM from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.39 MT-TM Zornitza Stark gene: MT-TM was added
gene: MT-TM was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TM.
Mode of inheritance for gene gene: MT-TM was set to MITOCHONDRIAL
Publications for gene: MT-TM were set to 9633749; 24711008; 25468263; 30739820; 11335700; 31488384; 31022467; 29174468
Phenotypes for gene: MT-TM were set to mitochondrial disease (MONDO:0044970), MT-TM-related
Mendeliome v1.4682 SLC26A5 Lucy Spencer reviewed gene: SLC26A5: Rating: AMBER; Mode of pathogenicity: None; Publications: 38431907, 38843436; Phenotypes: Deafness, autosomal recessive 61, MIM# 613865; Mode of inheritance: None
Mendeliome v1.4682 SLC19A1 Lucy Spencer Phenotypes for gene: SLC19A1 were changed from Megaloblastic anemia, folate-responsive, MIM# 601775; Combined immunodeficiency, SLC19A1-related MONDO:0015131 to Megaloblastic anemia, folate-responsive, MIM# 601775; Combined immunodeficiency, SLC19A1-related MONDO:0015131; myelomeningocele MONDO:0019773, SLC19A1-related
Mendeliome v1.4681 SLC19A1 Lucy Spencer reviewed gene: SLC19A1: Rating: RED; Mode of pathogenicity: None; Publications: 28948692; Phenotypes: myelomeningocele MONDO:0019773. SLC19A1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4681 WWP1 Sarah Milton gene: WWP1 was added
gene: WWP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WWP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WWP1 were set to 41786693; 32699206
Phenotypes for gene: WWP1 were set to Neurodevelopmental disorder, MONDO:0700092, WWP1-related
Review for gene: WWP1 was set to RED
Added comment: WWP1 encodes a E3 ubiquitin ligase involved in protein trafficking.

PMID: 32699206 describes 10 individuals with autism found to have missense or splice variants in WWP1 with an autism phenotype. Variants were all found to be inherited apart from 2 in which inheritance was unknown. Phenotypes of parents were not included in the publication. Authors propose variants in this gene are more common in neurodevelopmental cohorts than control populations.
All variants apart from 1 detected in affected individuals were present in gnomad v4, with allele frequencies ranging from 4 heterozygotes to 4000 heterozygotes.

PMID: 41786693 describes another affected individual with development epileptic encephalopathy and regression with a de novo missense in WWP1. This variant was present in 4 heterozygotes in gnomad v4.
Extensive functional studies were performed in this paper in mice and cell lines showing gain of function variants in WWP1 in mice embryos resulted in abnormal neuronal migration and increased neuronal apoptosis.

Further studies are needed to demonstrate a Mendelian gene disease association.
Sources: Literature
Early-onset Dementia v1.58 RBMX Lucy Spencer Publications for gene: RBMX were set to 25256757; 34260915; 37277488; 39263607
Ectodermal Dysplasia v0.110 RARG Zornitza Stark Marked gene: RARG as ready
Ectodermal Dysplasia v0.110 RARG Zornitza Stark Gene: rarg has been classified as Red List (Low Evidence).
Ectodermal Dysplasia v0.110 Zornitza Stark Copied gene RARG from panel Mendeliome
Ectodermal Dysplasia v0.110 RARG Zornitza Stark gene: RARG was added
gene: RARG was added to Ectodermal Dysplasia. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RARG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RARG were set to 41830175
Phenotypes for gene: RARG were set to Ectodermal dysplasia syndrome, MONDO:0019287, RARG-related
Early-onset Dementia v1.57 RBMX Lucy Spencer Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related to Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4680 RARG Zornitza Stark Marked gene: RARG as ready
Mendeliome v1.4680 RARG Zornitza Stark Gene: rarg has been classified as Red List (Low Evidence).
Mendeliome v1.4680 RARG Zornitza Stark changed review comment from: PMID 41830175 reports four affected members from a single family with a heterozygous truncating RARG variant (c.1237C>T, p.Arg413*) causing childhood‑onset urothelial keratinising squamous metaplasia (KDSM) and associated ectodermal features; the variant segregates in an autosomal‑dominant pattern and functional assays demonstrate dominant‑negative loss‑of‑function, but evidence is limited to one family.
Sources: Literature; to: PMID 41830175 reports four affected members from a single family with a heterozygous truncating RARG variant (c.1237C>T, p.Arg413*) causing childhood‑onset urothelial keratinising squamous metaplasia (KDSM) and associated ectodermal features. The truncating variant does not destabilise the transcript or protein produced from this allele but instead predicts the loss of half of helix 12 of RARγ, leading to reduced responsiveness of the receptor to all-trans retinoic acid via a dominant negative mechanism. Mice heterozygous for the variant demonstrated upregulation of cytokeratin-10 in the bladder and ureteric epithelium consistent with keratinising squamous metaplasia of the urothelium.
Sources: Literature
Mendeliome v1.4680 SIPA1L3 Lucy Spencer reviewed gene: SIPA1L3: Rating: AMBER; Mode of pathogenicity: None; Publications: 34603379; Phenotypes: Cataract 45 MIM#616851; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4680 RARG Zornitza Stark gene: RARG was added
gene: RARG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RARG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RARG were set to 41830175
Phenotypes for gene: RARG were set to Ectodermal dysplasia syndrome, MONDO:0019287, RARG-related
Review for gene: RARG was set to RED
Added comment: PMID 41830175 reports four affected members from a single family with a heterozygous truncating RARG variant (c.1237C>T, p.Arg413*) causing childhood‑onset urothelial keratinising squamous metaplasia (KDSM) and associated ectodermal features; the variant segregates in an autosomal‑dominant pattern and functional assays demonstrate dominant‑negative loss‑of‑function, but evidence is limited to one family.
Sources: Literature
Deafness_IsolatedAndComplex v1.349 NEU4 Zornitza Stark Marked gene: NEU4 as ready
Deafness_IsolatedAndComplex v1.349 NEU4 Zornitza Stark Gene: neu4 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.349 Zornitza Stark Copied gene NEU4 from panel Mendeliome
Deafness_IsolatedAndComplex v1.349 NEU4 Zornitza Stark gene: NEU4 was added
gene: NEU4 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NEU4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU4 were set to 41833579
Phenotypes for gene: NEU4 were set to Hearing loss disorder, MONDO:0005365, NEU4-related
Motor Neurone Disease v1.48 RBMX Lucy Spencer Phenotypes for gene: RBMX were changed from Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related to Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4679 NEU4 Zornitza Stark Marked gene: NEU4 as ready
Mendeliome v1.4679 NEU4 Zornitza Stark Gene: neu4 has been classified as Red List (Low Evidence).
Mendeliome v1.4679 NEU4 Zornitza Stark gene: NEU4 was added
gene: NEU4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NEU4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU4 were set to 41833579
Phenotypes for gene: NEU4 were set to Hearing loss disorder, MONDO:0005365, NEU4-related
Review for gene: NEU4 was set to RED
Added comment: NEU4 encodes neuraminidase‑14, a sialidase involved in neuraminic acid catabolism and neuronal development. PMID 41833579 reports 2 individuals from a single family with biallelic compound heterozygous missense variants presenting with congenital moderate sensorineural hearing loss. Functional assays demonstrated markedly reduced neuraminidase activity and Neu4‑/‑ mice displayed mild hearing loss, supporting pathogenicity.
Sources: Literature
Motor Neurone Disease v1.47 RBMX Lucy Spencer Publications for gene: RBMX were set to 39263607
Motor Neurone Disease v1.46 RBMX Lucy Spencer Publications for gene: RBMX were set to 25256757; 34260915; 37277488; 39263607
Motor Neurone Disease v1.46 RBMX Lucy Spencer Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related to Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4678 RPL9 Lucy Spencer Phenotypes for gene: RPL9 were changed from Diamond Blackfan anaemia to Diamond-Blackfan anaemia MONDO:0015253, RPL9-related
Mendeliome v1.4677 RPL9 Lucy Spencer Publications for gene: RPL9 were set to 29114930; 20116044; 31799629
Mendeliome v1.4676 RPL9 Lucy Spencer reviewed gene: RPL9: Rating: AMBER; Mode of pathogenicity: None; Publications: 34094714, 31799629, 29114930; Phenotypes: Diamond-Blackfan anaemia MONDO:0015253, RPL9-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.45 Lucy Spencer Copied gene RBMX from panel Mendeliome
Motor Neurone Disease v1.45 RBMX Lucy Spencer gene: RBMX was added
gene: RBMX was added to Motor Neurone Disease. Sources: Expert Review Amber,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; 37277488; 39263607
Phenotypes for gene: RBMX were set to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Early-onset Dementia v1.56 Lucy Spencer Copied gene RBMX from panel Mendeliome
Early-onset Dementia v1.56 RBMX Lucy Spencer gene: RBMX was added
gene: RBMX was added to Early-onset Dementia. Sources: Expert Review Amber,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; 37277488; 39263607
Phenotypes for gene: RBMX were set to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4676 RBMX Lucy Spencer Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4675 RBMX Lucy Spencer Publications for gene: RBMX were set to 25256757; 34260915; 37277488
Mendeliome v1.4674 RBMX Lucy Spencer reviewed gene: RBMX: Rating: AMBER; Mode of pathogenicity: None; Publications: 39263607; Phenotypes: Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Lysosomal Storage Disorder v1.31 AP5B1 Zornitza Stark Classified gene: AP5B1 as Green List (high evidence)
Lysosomal Storage Disorder v1.31 AP5B1 Zornitza Stark Gene: ap5b1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.60 AP5B1 Zornitza Stark Publications for gene: AP5B1 were set to 40081374
Macular Dystrophy/Stargardt Disease v0.59 AP5B1 Zornitza Stark Classified gene: AP5B1 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.59 AP5B1 Zornitza Stark Gene: ap5b1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.58 Zornitza Stark Added reviews for gene AP5B1 from panel Mendeliome
Lysosomal Storage Disorder v1.30 Zornitza Stark Added reviews for gene AP5B1 from panel Mendeliome
Mendeliome v1.4674 AP5B1 Zornitza Stark commented on gene: AP5B1: Two more families reported.
Mendeliome v1.4674 AP5B1 Zornitza Stark Publications for gene: AP5B1 were set to 40081374
Mendeliome v1.4673 AP5B1 Zornitza Stark Classified gene: AP5B1 as Green List (high evidence)
Mendeliome v1.4673 AP5B1 Zornitza Stark Gene: ap5b1 has been classified as Green List (High Evidence).
Mendeliome v1.4672 AP5B1 Zornitza Stark reviewed gene: AP5B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41830174; Phenotypes: Hereditary macular dystrophy MONDO:0020242, AP-5 complex-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.729 ASAH2 Zornitza Stark Marked gene: ASAH2 as ready
Intellectual disability syndromic and non-syndromic v1.729 ASAH2 Zornitza Stark Gene: asah2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.729 Zornitza Stark Copied gene ASAH2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.729 ASAH2 Zornitza Stark gene: ASAH2 was added
gene: ASAH2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ASAH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASAH2 were set to 41808410
Phenotypes for gene: ASAH2 were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4672 ASAH2 Zornitza Stark Marked gene: ASAH2 as ready
Mendeliome v1.4672 ASAH2 Zornitza Stark Gene: asah2 has been classified as Red List (Low Evidence).
Mendeliome v1.4672 ASAH2 Zornitza Stark gene: ASAH2 was added
gene: ASAH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ASAH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASAH2 were set to 41808410
Phenotypes for gene: ASAH2 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: ASAH2 was set to RED
Added comment: PMID 41808410 reports a single individual with biallelic loss-of-function (hypomorphic) missense variants presenting with a childhood-onset neurodevelopmental disorder characterized by cognitive impairment, neuropathy, ophthalmoplegia, and progressive cerebellar and extraocular muscle atrophy. Drosophila functional assays demonstrate reduced ASAH2 transcript and protein levels and neuromotor deficits, supporting loss-of-function.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.137 HIPK4 Zornitza Stark Marked gene: HIPK4 as ready
Infertility and Recurrent Pregnancy Loss v1.137 HIPK4 Zornitza Stark Gene: hipk4 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.137 Zornitza Stark Copied gene HIPK4 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.137 HIPK4 Zornitza Stark gene: HIPK4 was added
gene: HIPK4 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: HIPK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIPK4 were set to 10.64898/2026.03.04.26346694; 35931115
Phenotypes for gene: HIPK4 were set to Infertility disorder, MONDO:0005047, HIPK4-related
Mendeliome v1.4671 HIPK4 Zornitza Stark Marked gene: HIPK4 as ready
Mendeliome v1.4671 HIPK4 Zornitza Stark Gene: hipk4 has been classified as Green List (High Evidence).
Mendeliome v1.4671 HIPK4 Zornitza Stark Classified gene: HIPK4 as Green List (high evidence)
Mendeliome v1.4671 HIPK4 Zornitza Stark Gene: hipk4 has been classified as Green List (High Evidence).
Mendeliome v1.4670 HIPK4 Zornitza Stark gene: HIPK4 was added
gene: HIPK4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIPK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIPK4 were set to 10.64898/2026.03.04.26346694; 35931115
Phenotypes for gene: HIPK4 were set to Infertility disorder, MONDO:0005047, HIPK4-related
Review for gene: HIPK4 was set to GREEN
Added comment: PMID 35931115 reports 10 individuals from 10 unrelated families with heterozygous loss‑of‑function HIPK4 variants presenting with nonobstructive azoospermia; functional assays demonstrate reduced protein for a truncating variant and Hipk4 knockout mice are sterile, supporting a monoallelic loss‑of‑function disease mechanism.
Sources: Literature
Mendeliome v1.4669 TSEN54 Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.148 OCA2 Zornitza Stark Mode of inheritance for gene: OCA2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.147 OCA2 Zornitza Stark edited their review of gene: OCA2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4668 IGFBP7 Sangavi Sivagnanasundram reviewed gene: IGFBP7: Rating: AMBER; Mode of pathogenicity: None; Publications: 35299703, 35464689; Phenotypes: familial retinal arterial macroaneurysm, MONDO:0013640; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v1.18 PI4KA Eleanor Ludington gene: PI4KA was added
gene: PI4KA was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: PI4KA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4KA were set to PMID: 25855803
Phenotypes for gene: PI4KA were set to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531
Review for gene: PI4KA was set to AMBER
Added comment: 3 individuals from the same family described in PMID: 25855803 with biallelic PI4KA variants (nonsense variant and missense variant) presenting with arthrogryposis, polymicrogyria and cerebellar hypoplasia.
Sources: Literature
Mendeliome v1.4668 HAND1 Sangavi Sivagnanasundram changed review comment from: Additional reports of >5 unrelated probands with reported heterozygous variants in HAND1 (missense, promotor and 5'UTR variants)
Affected individuals presented with congenital heart disease, including septal defects, conotruncal malformations, tetralogy of Fallot, double outlet right ventricle, ventricular septal defect) of pediatric onset.

PMID:39107573 - Dual‑luciferase reporter assays for coding variants and luciferase/EMSA assays for promoter variants demonstrate loss‑of‑function of HAND1.; to: Additional reports of >5 unrelated probands with reported heterozygous variants in HAND1 (missense, promotor and 5'UTR variants)
Affected individuals presented with congenital heart disease, including septal defects, conotruncal malformations, tetralogy of Fallot, double outlet right ventricle, ventricular septal defect) of pediatric onset.

PMID:39107573 - Dual‑luciferase reporter assays for coding variants and luciferase/EMSA assays for promoter variants demonstrate loss‑of‑function of HAND1.

Classified as MODERATE by ClinGen Congenital Heart Disease GCEP on 04/04/2023 - https://search.clinicalgenome.org/CCID:005032
Congenital Heart Defect v0.534 Sangavi Sivagnanasundram Added reviews for gene HAND1 from panel Mendeliome
Mendeliome v1.4668 HAND1 Sangavi Sivagnanasundram reviewed gene: HAND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39537763, 39107573, 38551686; Phenotypes: congenital heart disease, MONDO:0005453; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v1.728 Sangavi Sivagnanasundram Added reviews for gene GTF2E2 from panel Mendeliome
Hair disorders v0.84 Sangavi Sivagnanasundram Added reviews for gene GTF2E2 from panel Mendeliome
Mendeliome v1.4668 GTF2E2 Sangavi Sivagnanasundram reviewed gene: GTF2E2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37793898, 31064989, 28973399; Phenotypes: trichothiodystrophy 6, nonphotosensitive, MONDO:0014841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v2.51 Sangavi Sivagnanasundram Added reviews for gene UQCRC1 from panel Incidentalome
Incidentalome v0.433 UQCRC1 Sangavi Sivagnanasundram reviewed gene: UQCRC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41783485, 39752790, 33141179, 33070102, 30788857; Phenotypes: Parkinsonism with polyneuropathy, MONDO:0036193; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.427 Sangavi Sivagnanasundram Added reviews for gene GNPNAT1 from panel Mendeliome
Mendeliome v1.4668 GNPNAT1 Sangavi Sivagnanasundram reviewed gene: GNPNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39945447, 36097642; Phenotypes: osteochondrodysplasia, MONDO:0005516; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.75 Sangavi Sivagnanasundram Added reviews for gene GAS2L2 from panel Mendeliome
Mendeliome v1.4668 GAS2L2 Sangavi Sivagnanasundram reviewed gene: GAS2L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36104176; Phenotypes: ciliary dyskinesia, primary, 41, MONDO:0032757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.727 ABCB7 Lucy Spencer Classified gene: ABCB7 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.727 ABCB7 Lucy Spencer Gene: abcb7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.726 ABCB7 Lucy Spencer gene: ABCB7 was added
gene: ABCB7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ABCB7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ABCB7 were set to 11050011; 26242992
Phenotypes for gene: ABCB7 were set to Anaemia, sideroblastic, with ataxia, MIM# 301310
Review for gene: ABCB7 was set to AMBER
Added comment: Some limited reports of developmental delay/ID in the literature and mentioned in the ClinGen review
Sources: Literature
Renal Tubulopathies and related disorders v1.26 Sangavi Sivagnanasundram Added reviews for gene FXYD2 from panel Mendeliome
Mendeliome v1.4668 FXYD2 Sangavi Sivagnanasundram changed review comment from: Classified as MODERATE by ClinGen Tubulopathy VCEP 29/06/2023 - https://search.clinicalgenome.org/CCID:004896 - this is based of the reports of a singular variant in multiple families

PMID: 40428357 - reports a Polish family (2 sibs and mother) presenting with hypercalciuria, glucosuria and mild proteinuria. The mother presented with a milder phenotype compared to the children.
c.80G>A, p.(Arg27His) - Variant is present in gnomAD v4.1 with global FAF - 0.00098% (23 hets globally)

Upgrade to green given a second variant that is shown to segregate in affected members of the family (siblings and mother); to: Classified as MODERATE by ClinGen Tubulopathy VCEP 29/06/2023 - https://search.clinicalgenome.org/CCID:004896 - this is based of the reports of a singular variant in multiple families

PMID: 40428357 - reports a Polish family (2 sibs and mother) presenting with hypercalciuria, glucosuria and mild proteinuria. The mother presented with a milder phenotype compared to the children.
c.80G>A, p.(Arg27His) - Variant is present in gnomAD v4.1 with global FAF - 0.00098% (23 hets globally)

Remain as Amber given that only two variants have been reported in affected individuals and no supportive functional evidence has been reported as of yet.
Mendeliome v1.4668 FXYD2 Sangavi Sivagnanasundram edited their review of gene: FXYD2: Changed rating: AMBER
Mendeliome v1.4668 FXYD2 Sangavi Sivagnanasundram reviewed gene: FXYD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 40428357; Phenotypes: Renal hypomagnesemia 2, MONDO:0007937; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Incidentalome v0.433 CCNF Bryony Thompson edited their review of gene: CCNF: Changed rating: AMBER
Differences of Sex Development v1.45 MARS2 Zornitza Stark Classified gene: MARS2 as Red List (low evidence)
Differences of Sex Development v1.45 MARS2 Zornitza Stark Gene: mars2 has been classified as Red List (Low Evidence).
Red cell disorders v1.52 BPGM Bryony Thompson Publications for gene: BPGM were set to 1421379; 27651169; 25015942
Red cell disorders v1.51 BPGM Bryony Thompson Mode of inheritance for gene: BPGM was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Red cell disorders v1.50 BPGM Bryony Thompson Classified gene: BPGM as Green List (high evidence)
Red cell disorders v1.50 BPGM Bryony Thompson Gene: bpgm has been classified as Green List (High Evidence).
Red cell disorders v1.49 Bryony Thompson Added reviews for gene BPGM from panel Mendeliome
Mendeliome v1.4668 BPGM Bryony Thompson Publications for gene: BPGM were set to 1421379; 27651169; 25015942
Mendeliome v1.4667 BPGM Bryony Thompson Mode of inheritance for gene: BPGM was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4666 BPGM Bryony Thompson Classified gene: BPGM as Green List (high evidence)
Mendeliome v1.4666 BPGM Bryony Thompson Gene: bpgm has been classified as Green List (High Evidence).
Mendeliome v1.4665 BPGM Bryony Thompson reviewed gene: BPGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 36177683, 35142155, 33216349, 29790589, 27651169; Phenotypes: hemolytic anemia due to diphosphoglycerate mutase deficiency, MONDO:0009113; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Skeletal dysplasia v0.426 Bryony Thompson Added reviews for gene BNIP1 from panel Mendeliome
Mendeliome v1.4665 BNIP1 Bryony Thompson edited their review of gene: BNIP1: Added comment: PMIDs 35266227 and 39706863 report a total of 3 unrelated families with homozygous hypomorphic BNIP1 variants with childhood‑onset spondylo‑epiphyseal dysplasia. Affected individuals present with disproportionate short stature, vertebral and epiphyseal abnormalities. Functional studies in the two families from PMID 35266227 demonstrate abnormal splicing, ~50% reduction of BNIP1 protein, accumulation of LC3B‑positive autophagosomes and impaired autophagic flux, supporting a loss‑of‑function mechanism. The third family adds an independent case without functional validation. No contradictory evidence is reported.; Changed publications: 39706863, 35266227; Changed phenotypes: Syndromic disease, MONDO:0002254
Pulmonary Arterial Hypertension v1.56 Bryony Thompson Added reviews for gene BMP10 from panel Mendeliome
Mendeliome v1.4665 BMP10 Bryony Thompson reviewed gene: BMP10: Rating: AMBER; Mode of pathogenicity: None; Publications: 38514094, 38322548, 36673052, 35737725, 33187088, 31243186, 30872557, 30578383; Phenotypes: pulmonary arterial hypertension, MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4665 CLN3 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association with ceroid lipofuscinosis.
Mendeliome v1.4665 CLN3 Zornitza Stark edited their review of gene: CLN3: Added comment: At least 20 families reported with isolated RP.; Changed publications: 7553855, 28542676, 33507216; Changed phenotypes: Ceroid lipofuscinosis, neuronal, 3, MIM# 204200, MONDO:0008767, Retinitis pigmentosa 101, MIM# 621548
Retinitis pigmentosa v0.245 CLN3 Zornitza Stark Marked gene: CLN3 as ready
Retinitis pigmentosa v0.245 CLN3 Zornitza Stark Gene: cln3 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.245 CLN3 Zornitza Stark Phenotypes for gene: CLN3 were changed from Retinitis pigmentosa; Juvenile neuronal ceroid lipofuscinosis to Retinitis pigmentosa 101, MIM# 621548
Retinitis pigmentosa v0.244 CLN3 Zornitza Stark Publications for gene: CLN3 were set to
Retinitis pigmentosa v0.243 CLN3 Zornitza Stark reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 101, MIM# 621548; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4665 DIO1 Bryony Thompson Publications for gene: DIO1 were set to
Deafness_IsolatedAndComplex v1.348 DIAPH3 Bryony Thompson Classified gene: DIAPH3 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.348 DIAPH3 Bryony Thompson Gene: diaph3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.347 DIAPH3 Bryony Thompson Publications for gene: DIAPH3 were set to 23441200; 20624953; 27658576; 38860500; 39767564
Deafness_IsolatedAndComplex v1.346 Bryony Thompson Added reviews for gene DIAPH3 from panel Mendeliome
Mendeliome v1.4664 DIAPH3 Bryony Thompson Classified gene: DIAPH3 as Green List (high evidence)
Mendeliome v1.4664 DIAPH3 Bryony Thompson Gene: diaph3 has been classified as Green List (High Evidence).
Mendeliome v1.4663 DIAPH3 Bryony Thompson reviewed gene: DIAPH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 41511813, 40040362, 38860500, 39767564, 20624953; Phenotypes: autosomal dominant auditory neuropathy 1, MONDO:0012196; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ocular and Oculocutaneous Albinism v1.16 OCA2 Zornitza Stark Mode of inheritance for gene: OCA2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ocular and Oculocutaneous Albinism v1.15 OCA2 Zornitza Stark edited their review of gene: OCA2: Added comment: OCA2 is now supported by 53 unrelated families (63 patients) across five studies. All families show autosomal recessive inheritance.; Changed publications: 32741191, 20301410, 38030918, 41807736, 31141302, 37650133, 41292147
Mendeliome v1.4663 OCA2 Zornitza Stark Phenotypes for gene: OCA2 were changed from Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous to Albinism, oculocutaneous, type II, MIM# 203200
Mendeliome v1.4662 OCA2 Zornitza Stark Publications for gene: OCA2 were set to 32741191; 24518832; 20301410
Mendeliome v1.4661 OCA2 Zornitza Stark Mode of inheritance for gene: OCA2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4660 OCA2 Zornitza Stark reviewed gene: OCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38030918, 41807736, 31141302, 37650133, 41292147; Phenotypes: Albinism, oculocutaneous, type II, MIM# 203200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4660 CTGF Bryony Thompson Mode of inheritance for gene: CTGF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4659 NLRP5 Zornitza Stark Phenotypes for gene: NLRP5 were changed from Early embryonic arrest; Multi locus imprinting disturbance in offspring to Early embryonic arrest; Multi locus imprinting disturbance in offspring; Oocyte/zygote/embryo maturation arrest 19, MIM# 620333
Mendeliome v1.4658 NLRP5 Zornitza Stark Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238; 26323243; 34440388
Mendeliome v1.4657 NLRP5 Zornitza Stark edited their review of gene: NLRP5: Added comment: PMID 39887367 reports 7 unrelated families with biallelic NLRP5 variants causing early embryonic arrest and female infertility; Changed publications: 32222962, 31829238, 30877238, 26323243, 34440388, 39887367; Changed phenotypes: Early embryonic arrest, Multi locus imprinting disturbance in offspring, Oocyte/zygote/embryo maturation arrest 19, MIM# 620333
Infertility and Recurrent Pregnancy Loss v1.136 NLRP5 Zornitza Stark Publications for gene: NLRP5 were set to 30877238; 32222962; 35091966; 35946397; 33583041
Infertility and Recurrent Pregnancy Loss v1.135 NLRP5 Zornitza Stark reviewed gene: NLRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 39887367; Phenotypes: Oocyte/zygote/embryo maturation arrest 19, MIM# 620333; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.554 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from Atrial septal defect 3 (MIM#614089) to Atrial septal defect 3 (MIM#614089); MYH-6 related congenital heart defects MONDO:0800442
Fetal anomalies v1.553 MYH6 Zornitza Stark Publications for gene: MYH6 were set to 20656787; 29969989; 15735645
Fetal anomalies v1.552 MYH6 Zornitza Stark Mode of inheritance for gene: MYH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.551 MYH6 Zornitza Stark reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28991257; Phenotypes: MYH-6 related congenital heart defects MONDO:0800442; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4657 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from Atrial septal defect 3 MIM#614089; Congenital heart disease; Cardiomyopathy, dilated, 1EE MIM#613252; Cardiomyopathy, hypertrophic, 14 MIM#613251; {Sick sinus syndrome 3} MIM#614090 to Atrial septal defect 3 MIM#614089; MYH-6 related congenital heart defects MONDO:0800442; Cardiomyopathy, dilated, 1EE MIM#613252; Cardiomyopathy, hypertrophic, 14 MIM#613251; {Sick sinus syndrome 3} MIM#614090
Mendeliome v1.4656 MYH6 Zornitza Stark Publications for gene: MYH6 were set to 32656206; 31638415; 29969989; 29536580; 29332214; 30681346
Mendeliome v1.4655 MYH6 Zornitza Stark Mode of inheritance for gene: MYH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4654 MYH6 Zornitza Stark changed review comment from: Please note the association with HCM has been rated as LIMITED by ClinGen.

There is a broader reported association with congenital heart disease beyond ASD.; to: Please note the association with HCM has been rated as LIMITED by ClinGen. The association with HCM is DISPUTED.

There is a broader reported association with congenital heart disease beyond ASD.
Mendeliome v1.4654 MYH6 Zornitza Stark edited their review of gene: MYH6: Added comment: PMID 28991257 reports 7 unrelated families with biallelic MYH6 variants (loss‑of‑function and missense alleles) causing Shone complex—a left‑ventricular outflow tract obstruction syndrome with mitral and aortic valve disease.; Changed publications: 32656206, 31638415, 29969989, 29536580, 29332214, 30681346, 28991257; Changed phenotypes: Atrial septal defect 3 MIM#614089, MYH-6 related congenital heart defects MONDO:0800442, Cardiomyopathy, dilated, 1EE MIM#613252, Cardiomyopathy, hypertrophic, 14 MIM#613251, {Sick sinus syndrome 3} MIM#614090; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.533 MYH6 Zornitza Stark Marked gene: MYH6 as ready
Congenital Heart Defect v0.533 MYH6 Zornitza Stark Gene: myh6 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.533 MYH6 Zornitza Stark Publications for gene: MYH6 were set to
Congenital Heart Defect v0.532 MYH6 Zornitza Stark Mode of inheritance for gene: MYH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.531 MYH6 Zornitza Stark reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28991257; Phenotypes: MYH-6 related congenital heart defects MONDO:0800442; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.551 KIF22 Zornitza Stark Publications for gene: KIF22 were set to 25256152; 22152677; 22152678
Fetal anomalies v1.550 KIF22 Zornitza Stark Mode of inheritance for gene: KIF22 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.549 KIF22 Zornitza Stark edited their review of gene: KIF22: Added comment: PMID 38477767 reports six individuals from six unrelated families (three with a homozygous c.146G>A p.Arg49Gln recessive variant and three with heterozygous c.443C>T p.Pro148Leu or c.446G>A p.Arg149Gln dominant variants) presenting with spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto‑SEMDJL). All patients display short stature, generalized joint laxity, multiple dislocations, scoliosis, and characteristic radiographic findings.

Evidence for recessive disease is limited to the one variant, albeit in three families (?founder).; Changed publications: 25256152, 38477767; Changed phenotypes: Spondyloepimetaphyseal dysplasia with joint laxity, type 2, MIM# 603546; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.425 KIF22 Zornitza Stark Marked gene: KIF22 as ready
Skeletal dysplasia v0.425 KIF22 Zornitza Stark Gene: kif22 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.425 KIF22 Zornitza Stark Phenotypes for gene: KIF22 were changed from Spondyloepimetaphyseal dysplasia with joint laxity, type 2 603546 to Spondyloepimetaphyseal dysplasia with joint laxity, type 2, MIM# 603546
Skeletal dysplasia v0.424 KIF22 Zornitza Stark Publications for gene: KIF22 were set to
Skeletal dysplasia v0.423 KIF22 Zornitza Stark Mode of inheritance for gene: KIF22 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.422 KIF22 Zornitza Stark edited their review of gene: KIF22: Added comment: PMID 38477767 reports six individuals from six unrelated families (three with a homozygous c.146G>A p.Arg49Gln recessive variant and three with heterozygous c.443C>T p.Pro148Leu or c.446G>A p.Arg149Gln dominant variants) presenting with spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto‑SEMDJL). All patients display short stature, generalized joint laxity, multiple dislocations, scoliosis, and characteristic radiographic findings.

Evidence for recessive disease is limited to the one variant, albeit in three families (?founder).; Changed publications: 25256152, 38477767; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.422 Zornitza Stark Added reviews for gene KIF22 from panel Mendeliome
Fetal anomalies v1.549 Zornitza Stark Added reviews for gene KIF22 from panel Mendeliome
Mendeliome v1.4654 KIF22 Zornitza Stark Publications for gene: KIF22 were set to 22152677; 22152678; 25256152
Mendeliome v1.4653 KIF22 Zornitza Stark Mode of inheritance for gene: KIF22 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4652 KIF22 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported with mono allelic disease.
Mendeliome v1.4652 KIF22 Zornitza Stark edited their review of gene: KIF22: Added comment: PMID 38477767 reports six individuals from six unrelated families (three with a homozygous c.146G>A p.Arg49Gln recessive variant and three with heterozygous c.443C>T p.Pro148Leu or c.446G>A p.Arg149Gln dominant variants) presenting with spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto‑SEMDJL). All patients display short stature, generalized joint laxity, multiple dislocations, scoliosis, and characteristic radiographic findings.

Evidence for recessive disease is limited to the one variant, albeit in three families (?founder).; Changed publications: 25256152, 38477767; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.135 GDF9 Zornitza Stark Publications for gene: GDF9 were set to 29044499; 33036707; 38643161
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.408 GDF9 Zornitza Stark Publications for gene: GDF9 were set to 29044499; 8849725; 33036707
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.407 Zornitza Stark Added reviews for gene GDF9 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.134 Zornitza Stark Added reviews for gene GDF9 from panel Mendeliome
Mendeliome v1.4652 GDF9 Zornitza Stark Publications for gene: GDF9 were set to 29044499; 8849725; 33036707
Mendeliome v1.4651 GDF9 Zornitza Stark edited their review of gene: GDF9: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4651 GDF9 Zornitza Stark reviewed gene: GDF9: Rating: GREEN; Mode of pathogenicity: None; Publications: 41783724, 38942181, 38672141, 38649916, 38643161, 35013061, 34095689, 33797006, 33538981, 33095795, 29044499, 27603904; Phenotypes: Premature ovarian failure 14, OMIM# 618014; Mode of inheritance: None
Mendeliome v1.4651 FOXI1 Zornitza Stark Phenotypes for gene: FOXI1 were changed from autosomal recessive distal renal tubular acidosis MONDO:0018440 to autosomal recessive distal renal tubular acidosis MONDO:0018440; Hearing loss disorder, MONDO:0005365, FOXI1-related
Mendeliome v1.4650 FOXI1 Zornitza Stark Publications for gene: FOXI1 were set to 9843211; 12642503; 29242249; 17503324; 30268946; 27997596; 22285650; 23965030; 24860705; 32447495; 19204907
Mendeliome v1.4649 FOXI1 Zornitza Stark Mode of inheritance for gene: FOXI1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4648 FOXI1 Zornitza Stark reviewed gene: FOXI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41833579, 27997596; Phenotypes: Hearing loss disorder, MONDO:0005365, FOXI1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.345 FOXI1 Zornitza Stark Phenotypes for gene: FOXI1 were changed from autosomal recessive distal renal tubular acidosis MONDO:0018440 to autosomal recessive distal renal tubular acidosis MONDO:0018440; Hearing loss disorder, MONDO:0005365, FOXI1-related
Deafness_IsolatedAndComplex v1.344 FOXI1 Zornitza Stark Publications for gene: FOXI1 were set to 9843211; 12642503; 29242249; 17503324; 30268946; 27997596; 22285650; 23965030; 24860705; 32447495; 19204907
Deafness_IsolatedAndComplex v1.343 FOXI1 Zornitza Stark Mode of inheritance for gene: FOXI1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.342 FOXI1 Zornitza Stark edited their review of gene: FOXI1: Added comment: PMID 41833579: reports 2 individuals from 2 unrelated families (F814 and F824) with a de novo heterozygous in‑frame deletion c.479_481del (p.Asn161del) presenting with Mondini malformation, enlarged vestibular aqueduct, and severe to profound sensorineural hearing loss. The variant is absent from gnomAD and other databases. Functional evidence includes a Foxi1 N155del/+ knock‑in mouse model that recapitulates cochlear dysplasia, EVA and elevated ABR thresholds, and luciferase reporter assays showing a dominant‑negative reduction of SLC26A4 promoter activity.

PMID 27997596 reports 2 unrelated individuals with heterozygous FOXI1 missense variants (c.519C>A de novo, c.716C>T) presenting with childhood‑onset sensorineural hearing loss and enlarged vestibular aqueduct. c.519C>A lies in the conserved forkhead DNA‑binding domain.; Changed rating: GREEN; Changed publications: 41833579, 27997596; Changed phenotypes: Hearing loss disorder, MONDO:0005365, FOXI1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic Diabetes v0.217 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related; neonatal diabetes
Monogenic Diabetes v0.216 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Monogenic Diabetes v0.215 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Monogenic Diabetes v0.215 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Monogenic Diabetes v0.214 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Changed publications: 41808409
Monogenic Diabetes v0.214 RNU6ATAC Zornitza Stark changed review comment from: PMID 40975062 reports 1 individual from with biallelic RNU6ATAC variants causing childhood‑onset growth restriction, microcephaly, epilepsy, intellectual disability and ataxia. PMID 41808409 reports 3 unrelated families (3 individuals) with biallelic loss‑of‑function RNU6ATAC variants presenting with short stature, neurodevelopmental delay, epilepsy, immunodeficiency, skeletal dysplasia and other multisystem features; RNA‑seq shows marked excess of minor intron retention, confirming spliceosome dysfunction.

However, note overlap in authors between the two papers ?double-counting.

PMID 41864208 -- published version of the preprint referenced in previous reviews. 7 individuals from 4 families with early-onset diabetes (diagnosed aged <5 years) and immune dysregulatory features caused by bi-allelic variants in RNU6ATAC.

Genotype-phenotype correlation unclear at this stage but note that of the three individuals reported in 41808409, one did not have ID/neurological features but all had immunological involvement.; to: PMID 41864208 -- published version of the preprint referenced in previous reviews. 7 individuals from 4 families with early-onset diabetes (diagnosed aged <5 years) and immune dysregulatory features caused by bi-allelic variants in RNU6ATAC.
Intellectual disability syndromic and non-syndromic v1.725 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related; neonatal diabetes
Intellectual disability syndromic and non-syndromic v1.724 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Intellectual disability syndromic and non-syndromic v1.723 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.723 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Genetic Epilepsy v1.398 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Genetic Epilepsy v1.397 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Genetic Epilepsy v1.396 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Genetic Epilepsy v1.396 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Monogenic Diabetes v0.214 Zornitza Stark Added reviews for gene RNU6ATAC from panel Mendeliome
Genetic Epilepsy v1.395 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Genetic Epilepsy v1.395 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.722 Zornitza Stark Added reviews for gene RNU6ATAC from panel Mendeliome
Genetic Epilepsy v1.394 Zornitza Stark Added reviews for gene RNU6ATAC from panel Mendeliome
Microcephaly v1.424 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Microcephaly v1.423 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Microcephaly v1.422 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Microcephaly v1.422 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Microcephaly v1.421 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Added comment: PMID 40975062 reports 1 individual from with biallelic RNU6ATAC variants causing childhood‑onset growth restriction, microcephaly, epilepsy, intellectual disability and ataxia. PMID 41808409 reports 3 unrelated families (3 individuals) with biallelic loss‑of‑function RNU6ATAC variants presenting with short stature, neurodevelopmental delay, epilepsy, immunodeficiency, skeletal dysplasia and other multisystem features; RNA‑seq shows marked excess of minor intron retention, confirming spliceosome dysfunction.

However, note overlap in authors between the two papers ?double-counting.

PMID 41864208 -- published version of the preprint referenced in previous reviews. 7 individuals from 4 families with early-onset diabetes (diagnosed aged <5 years) and immune dysregulatory features caused by bi-allelic variants in RNU6ATAC.

Genotype-phenotype correlation unclear at this stage but note that of the three individuals reported in 41808409, one did not have ID/neurological features but all had immunological involvement.; Changed rating: GREEN; Changed publications: 41808409, 40975062, 41864208; Changed phenotypes: Syndromic disease, MONDO:0002254, RNU6ATAC-related
Disorders of immune dysregulation v1.40 Zornitza Stark Copied gene RNU6ATAC from panel Mendeliome
Disorders of immune dysregulation v1.40 RNU6ATAC Zornitza Stark gene: RNU6ATAC was added
gene: RNU6ATAC was added to Disorders of immune dysregulation. Sources: Expert Review Green,Literature
non-coding gene tags were added to gene: RNU6ATAC.
Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU6ATAC were set to 41808409; 40975062; 41864208
Phenotypes for gene: RNU6ATAC were set to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Mendeliome v1.4648 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Mendeliome v1.4647 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Mendeliome v1.4646 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Mendeliome v1.4646 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Mendeliome v1.4645 RNU6ATAC Zornitza Stark reviewed gene: RNU6ATAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41808409, 40975062, 41864208; Phenotypes: Syndromic disease, MONDO:0002254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4645 Bryony Thompson Added reviews for gene ERG from panel Bone Marrow Failure
Leukodystrophy v0.393 Rylee Peters Added reviews for gene PLEKHG2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.721 Rylee Peters Added reviews for gene PLEKHG2 from panel Mendeliome
Mendeliome v1.4644 PLEKHG2 Rylee Peters Publications for gene: PLEKHG2 were set to 26573021
Mendeliome v1.4643 PLEKHG2 Rylee Peters reviewed gene: PLEKHG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 40594583; Phenotypes: Leukodystrophy and acquired microcephaly with or without dystonia, MIM# 616763; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4643 OXA1L Rylee Peters reviewed gene: OXA1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 40551575, 30201738; Phenotypes: Combined oxidative phosphorylation deficiency (MONDO:0000732), OXA1L-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.63 OPN1MW Rylee Peters Classified gene: OPN1MW as Green List (high evidence)
Cone-rod Dystrophy v0.63 OPN1MW Rylee Peters Gene: opn1mw has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.62 Rylee Peters Added reviews for gene OPN1MW from panel Mendeliome
Mendeliome v1.4643 OPN1MW Rylee Peters Classified gene: OPN1MW as Green List (high evidence)
Mendeliome v1.4643 OPN1MW Rylee Peters Gene: opn1mw has been classified as Green List (High Evidence).
Mendeliome v1.4642 OPN1MW Rylee Peters changed review comment from: Green rating for Colorblindness, deutan, MIM#303800

OPN1MW is Definitively associated with OPN1MW-related cone dysfunction - classification was approved by the ClinGen Retina Gene Curation Expert Panel on September 4th, 2025.

OPN1LW is definitively associated with OPN1LW-related cone dysfunction - classification was approved by the ClinGen Retina Gene Curation Expert Panel on September 4th, 2025.

"Per criteria outlined by the ClinGen Lumping & Splitting Working Group, diverse cases were compared and found to share an X-linked mode of inheritance and a degree of overlap in their phenotypes, but to differ in the mechanism of pathogenicity underlying deutan color blindness (monogenic OPN1MW loss-of-function) versus blue cone monochromacy (digenic OPN1MW and OPN1LW loss-of-function)."; to: Green rating for Colorblindness, deutan, MIM#303800

OPN1MW is Definitively associated with OPN1MW-related cone dysfunction - classification was approved by the ClinGen Retina Gene Curation Expert Panel on September 4th, 2025.

"Per criteria outlined by the ClinGen Lumping & Splitting Working Group, diverse cases were compared and found to share an X-linked mode of inheritance and a degree of overlap in their phenotypes, but to differ in the mechanism of pathogenicity underlying deutan color blindness (monogenic OPN1MW loss-of-function) versus blue cone monochromacy (digenic OPN1MW and OPN1LW loss-of-function)."
Mendeliome v1.4642 OPN1MW Rylee Peters reviewed gene: OPN1MW: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Colorblindness, deutan, MIM#303800; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cone-rod Dystrophy v0.61 OPN1LW Rylee Peters Classified gene: OPN1LW as Green List (high evidence)
Cone-rod Dystrophy v0.61 OPN1LW Rylee Peters Gene: opn1lw has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.60 Rylee Peters Added reviews for gene OPN1LW from panel Mendeliome
Mendeliome v1.4642 OPN1LW Rylee Peters Classified gene: OPN1LW as Green List (high evidence)
Mendeliome v1.4642 OPN1LW Rylee Peters Gene: opn1lw has been classified as Green List (High Evidence).
Mendeliome v1.4641 OPN1LW Rylee Peters reviewed gene: OPN1LW: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Colorblindness, protan, MIM#303900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Gastrointestinal neuromuscular disease v1.26 Rylee Peters Added reviews for gene NRG1 from panel Mendeliome
Mendeliome v1.4641 NRG1 Rylee Peters Mode of inheritance for gene: NRG1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4640 NRG1 Rylee Peters Phenotypes for gene: NRG1 were changed from Hirschsprung disease, MONDO:0018309; Peripheral neuropathy MONDO:0005244 to Hirschsprung disease, susceptibility (MONDO:0100179), NRG1-related; Peripheral neuropathy MONDO:0005244
Mendeliome v1.4639 NRG1 Rylee Peters Publications for gene: NRG1 were set to 22574178; 21706185; 28190554
Mendeliome v1.4638 NRG1 Rylee Peters reviewed gene: NRG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33421311, 31240788; Phenotypes: Hirschsprung disease, susceptibility (MONDO:0100179), NRG1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.393 Rylee Peters Added reviews for gene NECAP1 from panel Mendeliome
Mendeliome v1.4638 NECAP1 Rylee Peters reviewed gene: NECAP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35638367; Phenotypes: Developmental and epileptic encephalopathy 21, MIM#615833; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.548 Rylee Peters Added reviews for gene MMP15 from panel Mendeliome
Cholestasis v1.10 Rylee Peters Added reviews for gene MMP15 from panel Mendeliome
Mendeliome v1.4638 MMP15 Rylee Peters Publications for gene: MMP15 were set to 33875846
Mendeliome v1.4637 MMP15 Rylee Peters reviewed gene: MMP15: Rating: AMBER; Mode of pathogenicity: None; Publications: 36349822; Phenotypes: Progressive familial intrahepatic cholestasis, MONDO:0015762, MMP15-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4637 PADI6 Bryony Thompson Publications for gene: PADI6 were set to 29693651; 33583041; 329228291; 33221824; 27545678
Mendeliome v1.4636 NLRP5 Bryony Thompson Publications for gene: NLRP5 were set to 32232222962; 31829238; 30877238; 26323243; 34440388
Mendeliome v1.4635 AMELX Bryony Thompson Publications for gene: AMELX were set to 17189466; 22243263; 7599636; 23251683; 1483698 1916828; 9188994; 15111628; 11201048; 26502894; 7782077; 11922869; 28130977; 8406474; 11839357; 25117480; 19610109
Mendeliome v1.4634 ZBTB26 Chirag Patel Marked gene: ZBTB26 as ready
Mendeliome v1.4634 ZBTB26 Chirag Patel Gene: zbtb26 has been classified as Green List (High Evidence).
Mendeliome v1.4634 Chirag Patel Copied gene ZBTB26 from panel Congenital hypothyroidism
Mendeliome v1.4634 ZBTB26 Chirag Patel gene: ZBTB26 was added
gene: ZBTB26 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ZBTB26 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZBTB26 were set to 34946811
Phenotypes for gene: ZBTB26 were set to Congenital hypothyroidism MONDO:0018612
Congenital hypothyroidism v0.117 ZBTB26 Chirag Patel Marked gene: ZBTB26 as ready
Congenital hypothyroidism v0.117 ZBTB26 Chirag Patel Gene: zbtb26 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.117 ZBTB26 Chirag Patel Classified gene: ZBTB26 as Green List (high evidence)
Congenital hypothyroidism v0.117 ZBTB26 Chirag Patel Gene: zbtb26 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.116 ZBTB26 Chirag Patel gene: ZBTB26 was added
gene: ZBTB26 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: ZBTB26 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZBTB26 were set to 34946811
Phenotypes for gene: ZBTB26 were set to Congenital hypothyroidism MONDO:0018612
Review for gene: ZBTB26 was set to GREEN
Added comment: PMID 34946811 reports 3 individuals from 3 unrelated families with heterozygous ZBTB26 variants (2 x missense and 1 x splice‑proximal) presenting with congenital primary hypothyroidism. De novo status confirmed for 1 patient but parental status unavailable for 2 patients. Xenopus loss‑of‑function studies recapitulated the phenotype and were rescued by wild‑type mRNA, supporting a loss‑of‑function mechanism.
Sources: Literature
Congenital hypothyroidism v0.115 UBR7 Chirag Patel Marked gene: UBR7 as ready
Congenital hypothyroidism v0.115 UBR7 Chirag Patel Gene: ubr7 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.115 Chirag Patel Copied gene UBR7 from panel Mendeliome
Congenital hypothyroidism v0.115 UBR7 Chirag Patel gene: UBR7 was added
gene: UBR7 was added to Congenital hypothyroidism. Sources: Expert Review Green,Literature
Mode of inheritance for gene: UBR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBR7 were set to 33340455
Phenotypes for gene: UBR7 were set to Li-Campeau syndrome, MIM# 619189; Intellectual disability; epilepsy; hypothyroidism; congenital anomalies; dysmorphic features
Genetic Epilepsy v1.392 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339; 38705457
Genetic Epilepsy v1.391 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339; 38705457
Genetic Epilepsy v1.391 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339; 38705457
Genetic Epilepsy v1.391 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339
Congenital hypothyroidism v0.114 TANGO2 Chirag Patel Marked gene: TANGO2 as ready
Congenital hypothyroidism v0.114 TANGO2 Chirag Patel Gene: tango2 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.114 TANGO2 Chirag Patel Publications for gene: TANGO2 were set to 26805782; 30245509
Congenital hypothyroidism v0.113 TANGO2 Chirag Patel Deleted their comment
Congenital hypothyroidism v0.113 TANGO2 Chirag Patel edited their review of gene: TANGO2: Added comment: hypothyroidism noted in 12/20 (PMID: 32929747) and 31/65 (PMID: 36473599) patients but unclear of age of onset.; Changed rating: AMBER; Changed publications: 36473599 32929747
Congenital hypothyroidism v0.113 TANGO2 Chirag Patel Classified gene: TANGO2 as Amber List (moderate evidence)
Congenital hypothyroidism v0.113 TANGO2 Chirag Patel Gene: tango2 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.112 TANGO2 Chirag Patel Classified gene: TANGO2 as Red List (low evidence)
Congenital hypothyroidism v0.112 TANGO2 Chirag Patel Gene: tango2 has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.111 TANGO2 Chirag Patel reviewed gene: TANGO2: Rating: RED; Mode of pathogenicity: None; Publications: 36473599, 32929747; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.390 Rylee Peters Added reviews for gene MICAL1 from panel Mendeliome
Deafness_IsolatedAndComplex v1.342 DLX5 Zornitza Stark Marked gene: DLX5 as ready
Deafness_IsolatedAndComplex v1.342 DLX5 Zornitza Stark Gene: dlx5 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.342 DLX5 Zornitza Stark Classified gene: DLX5 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.342 DLX5 Zornitza Stark Gene: dlx5 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.111 Chirag Patel Copied gene TANGO2 from panel Mendeliome
Congenital hypothyroidism v0.111 TANGO2 Chirag Patel gene: TANGO2 was added
gene: TANGO2 was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TANGO2 were set to 26805782; 30245509
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
Deafness_IsolatedAndComplex v1.341 DLX5 Zornitza Stark gene: DLX5 was added
gene: DLX5 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: DLX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLX5 were set to 41760400; 22121204
Phenotypes for gene: DLX5 were set to Split-hand/foot malformation 1 with sensorineural hearing loss, MIM# 220600
Review for gene: DLX5 was set to AMBER
Added comment: Two families reported with bi-allelic variants and SHFM/SNHL.
Sources: Literature
Mendeliome v1.4633 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339
Mendeliome v1.4632 MICAL1 Rylee Peters reviewed gene: MICAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38705457, 29394500; Phenotypes: Epilepsy, MONDO:0005027, MICAL1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital hypothyroidism v0.110 SGPL1 Chirag Patel Marked gene: SGPL1 as ready
Congenital hypothyroidism v0.110 SGPL1 Chirag Patel Gene: sgpl1 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.110 SGPL1 Chirag Patel Publications for gene: SGPL1 were set to 33074640
Fetal anomalies v1.547 DLX5 Zornitza Stark Publications for gene: DLX5 were set to 22121204; 24496061; 25196357; 20534536; 12112878
Congenital hypothyroidism v0.109 SGPL1 Chirag Patel reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35904228, 35748945, 32322566, 28165343, 38204317; Phenotypes: Sphingosine phosphate lyase insufficiency syndrome (SPLIS); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.546 DLX5 Zornitza Stark reviewed gene: DLX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 41760400; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hand and foot malformations v0.85 DLX5 Zornitza Stark Marked gene: DLX5 as ready
Hand and foot malformations v0.85 DLX5 Zornitza Stark Gene: dlx5 has been classified as Green List (High Evidence).
Hand and foot malformations v0.85 DLX5 Zornitza Stark Publications for gene: DLX5 were set to
Hand and foot malformations v0.84 DLX5 Zornitza Stark edited their review of gene: DLX5: Added comment: PMID 41760400 adds a new family with a homozygous nonsense DLX5 variant c.97G>T (NM_005221.6) causing autosomal recessive split‑hand/foot malformation type 1D (SHFM1D) accompanied by hypospadias, sensorineural hearing loss and atrial septal defect; Changed publications: 41760400
Skeletal dysplasia v0.421 DLX5 Zornitza Stark Marked gene: DLX5 as ready
Skeletal dysplasia v0.421 DLX5 Zornitza Stark Gene: dlx5 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.421 DLX5 Zornitza Stark Publications for gene: DLX5 were set to 27085093
Skeletal dysplasia v0.420 DLX5 Zornitza Stark edited their review of gene: DLX5: Added comment: PMID 41760400 adds a new family with a homozygous nonsense DLX5 variant c.97G>T (NM_005221.6) causing autosomal recessive split‑hand/foot malformation type 1D (SHFM1D) accompanied by hypospadias, sensorineural hearing loss and atrial septal defect; Changed publications: 41760400
Mendeliome v1.4632 DLX5 Zornitza Stark Publications for gene: DLX5 were set to 22121204; 24496061; 25196357; 20534536; 12112878
Mendeliome v1.4631 DLX5 Zornitza Stark edited their review of gene: DLX5: Added comment: PMID 41760400 adds a new family with a homozygous nonsense DLX5 variant c.97G>T (NM_005221.6) causing autosomal recessive split‑hand/foot malformation type 1D (SHFM1D) accompanied by hypospadias, sensorineural hearing loss and atrial septal defect; Changed publications: 22121204, 24496061, 25196357, 20534536, 12112878, 41760400
Congenital hypothyroidism v0.109 Chirag Patel Copied gene SGPL1 from panel Adrenal insufficiency
Congenital hypothyroidism v0.109 SGPL1 Chirag Patel gene: SGPL1 was added
gene: SGPL1 was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to 33074640
Phenotypes for gene: SGPL1 were set to RENI syndrome (MIM#617575)
Intellectual disability syndromic and non-syndromic v1.720 RNPC3 Chirag Patel Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182
Congenital hypothyroidism v0.108 RNPC3 Chirag Patel Marked gene: RNPC3 as ready
Congenital hypothyroidism v0.108 RNPC3 Chirag Patel Gene: rnpc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.720 RNPC3 Chirag Patel Classified gene: RNPC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.720 RNPC3 Chirag Patel Gene: rnpc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.719 RNPC3 Chirag Patel Classified gene: RNPC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.719 RNPC3 Chirag Patel Gene: rnpc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.719 RNPC3 Chirag Patel Classified gene: RNPC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.719 RNPC3 Chirag Patel Gene: rnpc3 has been classified as Green List (High Evidence).
Mendeliome v1.4631 RNPC3 Chirag Patel Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182
Growth failure v1.101 RNPC3 Chirag Patel Publications for gene: RNPC3 were set to 32462814; 29866761; 24480542; 33650182
Mendeliome v1.4630 Chirag Patel Added reviews for gene RNPC3 from panel Pituitary hormone deficiency
Intellectual disability syndromic and non-syndromic v1.718 Chirag Patel Added reviews for gene RNPC3 from panel Pituitary hormone deficiency
Growth failure v1.100 Chirag Patel Added reviews for gene RNPC3 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.108 Chirag Patel Copied gene RNPC3 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.108 RNPC3 Chirag Patel gene: RNPC3 was added
gene: RNPC3 was added to Congenital hypothyroidism. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182; 37463572; 35792517; 34906446
Phenotypes for gene: RNPC3 were set to Growth hormone deficiency; Intellectual disability
Pituitary hormone deficiency v0.199 RNPC3 Chirag Patel Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182
Pituitary hormone deficiency v0.198 RNPC3 Chirag Patel reviewed gene: RNPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37463572, 35792517, 34906446; Phenotypes: Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.198 RNPC3 Chirag Patel Deleted their review
Pituitary hormone deficiency v0.198 RNPC3 Chirag Patel reviewed gene: RNPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37463572, 35792517; Phenotypes: Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4629 KCNH5 Bryony Thompson Publications for gene: KCNH5 were set to https://www.medrxiv.org/content/10.1101/2022.04.26.22274147v1
Susceptibility to Viral Infections v1.10 DOCK2 Zornitza Stark Phenotypes for gene: DOCK2 were changed from Inborn error of immunity, MONDO:0003778, DOC2-related to Inborn error of immunity, MONDO:0003778, DOCK2-related
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark edited their review of gene: DOCK2: Changed phenotypes: Inborn error of immunity, MONDO:0003778, DOCK2-related
Mendeliome v1.4628 DOCK2 Zornitza Stark Phenotypes for gene: DOCK2 were changed from Immunodeficiency 40 MIM# 616433; T/B-cell lymphopaenia; early-onset invasive herpes/viral/bacterial Infections; function defects in T/B/NK cells; immunodeficiency; defective IFN-mediated immunity; elevated IgM; normal IgG/IgA levels to Immunodeficiency 40 MIM# 616433; Inborn error of immunity, MONDO:0003778, DOCK2-related
Mendeliome v1.4627 DOCK2 Zornitza Stark Publications for gene: DOCK2 were set to 26083206; 29204803; 33928462; 30826364; 30838481; 11518968
Mendeliome v1.4626 DOCK2 Zornitza Stark Mode of inheritance for gene: DOCK2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4625 DOCK2 Zornitza Stark changed review comment from: 13 unrelated individuals; two mouse models; 10 biallelic mutations found (6 led to premature termination of the protein & 4 missense mutations affecting conserved residues) All patients presented with combined immunodeficiency in infancy (defective IFN-mediated immunity), early onset of invasive bacterial and viral infections, functional defects in T/B/NK cells and elevated IgM (normal IgG/IgA).; to: Bi-allelic disease: 13 unrelated individuals; two mouse models; 10 biallelic mutations found (6 led to premature termination of the protein & 4 missense mutations affecting conserved residues) All patients presented with combined immunodeficiency in infancy (defective IFN-mediated immunity), early onset of invasive bacterial and viral infections, functional defects in T/B/NK cells and elevated IgM (normal IgG/IgA).
Mendeliome v1.4625 DOCK2 Zornitza Stark edited their review of gene: DOCK2: Added comment: PMID 41654261: Six individuals from three unrelated families, aged 3 months to 50 years, reported with one of three heterozygous variants in DOCK2 and severe infections with human papilloma virus, respiratory syncytial virus, or SARS-CoV-2. All variants reside within the DOCK2 domain that binds and stabilizes ELMO1. Each variant reduced DOCK2 protein expression, ELMO1 binding, and DOCK2 function, as shown by diminished Rac1 activation and selective defects in Toll-like receptor signaling. Weekly IFN-α therapy led to complete resolution of refractory warts in one patient, highlighting a potential therapeutic approach for DOCK2-associated immunodeficiency.

PMID 36836791: Patient with recurrent HLH. Heterozygous c.1334A>G (p.Asn445Ser) variant. Functional studies showing lower CD107a expression and diminished NK degranulation and cytotoxicity. ? partial dominant negative.; Changed publications: 26083206, 29204803, 33928462, 30826364, 30838481, 11518968, 41654261, 36836791; Changed phenotypes: Immunodeficiency 40 MIM# 616433, Inborn error of immunity, MONDO:0003778, DOCK2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark Classified gene: DOCK2 as Green List (high evidence)
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.99 PROKR2 Chirag Patel Deleted their comment
Pituitary hormone deficiency v0.198 PROKR2 Chirag Patel Deleted their comment
Congenital hypothyroidism v0.107 POMC Chirag Patel Publications for gene: POMC were set to 33666293
Pituitary hormone deficiency v0.198 POMC Chirag Patel Publications for gene: POMC were set to 33666293
Pituitary hormone deficiency v0.197 POMC Chirag Patel Marked gene: POMC as ready
Pituitary hormone deficiency v0.197 POMC Chirag Patel Gene: pomc has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.197 POMC Chirag Patel reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: 40513101, 34177811, 29858905; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v0.106 POMC Chirag Patel Marked gene: POMC as ready
Congenital hypothyroidism v0.106 POMC Chirag Patel Gene: pomc has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.106 POMC Chirag Patel reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: 40513101, 34177811, 29858905; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.197 Chirag Patel Copied gene POMC from panel Mendeliome
Pituitary hormone deficiency v0.197 POMC Chirag Patel gene: POMC was added
gene: POMC was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POMC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMC were set to 33666293
Phenotypes for gene: POMC were set to Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734
Congenital hypothyroidism v0.106 Chirag Patel Copied gene POMC from panel Mendeliome
Congenital hypothyroidism v0.106 POMC Chirag Patel gene: POMC was added
gene: POMC was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POMC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMC were set to 33666293
Phenotypes for gene: POMC were set to Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734
Susceptibility to Viral Infections v1.8 DOCK2 Zornitza Stark gene: DOCK2 was added
gene: DOCK2 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: DOCK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOCK2 were set to 41654261
Phenotypes for gene: DOCK2 were set to Inborn error of immunity, MONDO:0003778, DOC2-related
Review for gene: DOCK2 was set to GREEN
Added comment: Six individuals from three unrelated families, aged 3 months to 50 years, reported with one of three heterozygous variants in DOCK2 and severe infections with human papilloma virus, respiratory syncytial virus, or SARS-CoV-2. All variants reside within the DOCK2 domain that binds and stabilizes ELMO1. Each variant reduced DOCK2 protein expression, ELMO1 binding, and DOCK2 function, as shown by diminished Rac1 activation and selective defects in Toll-like receptor signaling. Weekly IFN-α therapy led to complete resolution of refractory warts in one patient, highlighting a potential therapeutic approach for DOCK2-associated immunodeficiency.
Sources: Literature
Skeletal dysplasia v0.420 POC1A Chirag Patel Marked gene: POC1A as ready
Skeletal dysplasia v0.420 POC1A Chirag Patel Gene: poc1a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.419 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis 614813; Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis 614813 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.419 POC1A Chirag Patel Publications for gene: POC1A were set to 22840364; 22840363; 26374189; 26162852; 26791357; 39662966
Skeletal dysplasia v0.419 POC1A Chirag Patel Publications for gene: POC1A were set to 26374189; 26162852; 26336158
Skeletal dysplasia v0.418 POC1A Chirag Patel reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39662966; Phenotypes: Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.717 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.716 POC1A Chirag Patel Publications for gene: POC1A were set to
Intellectual disability syndromic and non-syndromic v1.715 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.715 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.715 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.715 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM#614813 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.714 POC1A Chirag Patel Classified gene: POC1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.714 POC1A Chirag Patel Gene: poc1a has been classified as Green List (High Evidence).
Hand and foot malformations v0.84 Sarah Milton Copied Region PITX1 upstream regulatory region from panel Mendeliome
Hand and foot malformations v0.84 PITX1 upstream regulatory region Sarah Milton Region: PITX1 upstream regulatory region was added
Region: PITX1 upstream regulatory region was added to Hand and foot malformations. Sources: Literature
Mode of inheritance for Region: PITX1 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: PITX1 upstream regulatory region were set to PMID: 30711920; 23022097; 25124102; 23587911
Phenotypes for Region: PITX1 upstream regulatory region were set to Liebenberg syndrome, MIM#186550
Intellectual disability syndromic and non-syndromic v1.714 POC1A Chirag Patel Classified gene: POC1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.714 POC1A Chirag Patel Gene: poc1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.713 POC1A Chirag Patel reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39662966; Phenotypes: Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4625 PITX1 upstream regulatory region Sarah Milton Region: PITX1 upstream regulatory region was added
Region: PITX1 upstream regulatory region was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: PITX1 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: PITX1 upstream regulatory region were set to PMID: 30711920; 23022097; 25124102; 23587911
Phenotypes for Region: PITX1 upstream regulatory region were set to Liebenberg syndrome, MIM#186550
Review for Region: PITX1 upstream regulatory region was set to GREEN
Added comment: PITX1 is a transcription factor expressed solely in the hindlimb during limb development where it ensures proper outgrowth and patterning of this tissue.

Over 25 individuals have been reported in the literature with deletions upstream of PITX1 presenting with Liebenberg syndrome characterised by dysplastic elbow joints and the fusion of wrist bones and the consequent radial deviation. With upper limb features resembling some of those seen in the lower limb.

The deletions seen in affected individuals range from 8kb to 134kb in size and are thought to result in overexpression of PITX1 by affecting the proximity between the coding sequence and an upstream enhancer (referred to variably as 'Pen' or 'hs1473').
The deletion removes part of a different protein coding gene - MACROH2A1 which is not thought to contribute to the pathogenesis (knockout mice do not present with a similar phenotype to Liebenberg).
Authors of PMID: 30711920 suggest the promoter of MACROH2A1 acts as an insulator between the upstream enhancer and PITX1 however further functional studies are required to establish this.

Functional studies involving transgenic mice with the enhancer element just upstream of PITX1 resulting in a similar phenotype to affected individuals.

Note: Maximal reported deletion coordinates at time of writing: chr5:135288912-135423802
Minimum: chr5:135393716-135402219:
Sources: Literature
Monogenic Diabetes v0.213 POC1A Chirag Patel Publications for gene: POC1A were set to 22840364; 22840363; 26374189; 26162852; 26791357
Monogenic Diabetes v0.212 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Monogenic Diabetes v0.211 POC1A Chirag Patel reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39662966; Phenotypes: Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.211 Chirag Patel Copied gene POC1A from panel Mendeliome
Monogenic Diabetes v0.211 POC1A Chirag Patel gene: POC1A was added
gene: POC1A was added to Monogenic Diabetes. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POC1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POC1A were set to 22840364; 22840363; 26374189; 26162852; 26791357
Phenotypes for gene: POC1A were set to Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813
Intellectual disability syndromic and non-syndromic v1.713 Chirag Patel Added reviews for gene POC1A from panel Mendeliome
Pituitary hormone deficiency v0.196 PCSK1 Chirag Patel Marked gene: PCSK1 as ready
Pituitary hormone deficiency v0.196 PCSK1 Chirag Patel Gene: pcsk1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.99 PCSK1 Chirag Patel Marked gene: PCSK1 as ready
Hypogonadotropic hypogonadism v0.99 PCSK1 Chirag Patel Gene: pcsk1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.196 Chirag Patel Copied gene PCSK1 from panel Adrenal insufficiency
Pituitary hormone deficiency v0.196 PCSK1 Chirag Patel gene: PCSK1 was added
gene: PCSK1 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCSK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCSK1 were set to 30383237
Phenotypes for gene: PCSK1 were set to Obesity with impaired prohormone processing MIM#600955
Hypogonadotropic hypogonadism v0.99 Chirag Patel Copied gene PCSK1 from panel Adrenal insufficiency
Hypogonadotropic hypogonadism v0.99 PCSK1 Chirag Patel gene: PCSK1 was added
gene: PCSK1 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCSK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCSK1 were set to 30383237
Phenotypes for gene: PCSK1 were set to Obesity with impaired prohormone processing MIM#600955
Adrenal insufficiency v0.76 PCSK1 Chirag Patel changed review comment from: adrenal insufficiency seen in condition; to: Various endocrine disorders present as disease progresses, including GH deficiency (44%), mild central hypothyroidism (56%), central hypogonadism (44%), central hypocortisolism (57%), and postprandial hypoglycemia (52%).
Congenital hypothyroidism v0.105 NUDCD2 Chirag Patel Marked gene: NUDCD2 as ready
Congenital hypothyroidism v0.105 NUDCD2 Chirag Patel Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Cholestasis v1.9 NUDCD2 Chirag Patel Marked gene: NUDCD2 as ready
Cholestasis v1.9 NUDCD2 Chirag Patel Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.99 NUDCD2 Chirag Patel Marked gene: NUDCD2 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.99 NUDCD2 Chirag Patel Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.546 Chirag Patel Added reviews for gene NUDCD2 from panel Mendeliome
Congenital hypothyroidism v0.105 Chirag Patel Copied gene NUDCD2 from panel Mendeliome
Congenital hypothyroidism v0.105 NUDCD2 Chirag Patel gene: NUDCD2 was added
gene: NUDCD2 was added to Congenital hypothyroidism. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Cholestasis v1.9 Chirag Patel Copied gene NUDCD2 from panel Mendeliome
Cholestasis v1.9 NUDCD2 Chirag Patel gene: NUDCD2 was added
gene: NUDCD2 was added to Cholestasis. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Cerebellar and Pontocerebellar Hypoplasia v1.99 Chirag Patel Copied gene NUDCD2 from panel Mendeliome
Cerebellar and Pontocerebellar Hypoplasia v1.99 NUDCD2 Chirag Patel gene: NUDCD2 was added
gene: NUDCD2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Mendeliome v1.4624 NUDCD2 Chirag Patel reviewed gene: NUDCD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37272762; Phenotypes: Multiple congenital anomalies (MONDO:0019042), NUDCD2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v0.98 POLR3A Chirag Patel Marked gene: POLR3A as ready
Hypogonadotropic hypogonadism v0.98 POLR3A Chirag Patel Gene: polr3a has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 PNPLA6 Chirag Patel Marked gene: PNPLA6 as ready
Hypogonadotropic hypogonadism v0.98 PNPLA6 Chirag Patel Gene: pnpla6 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 PLXNA3 Chirag Patel Marked gene: PLXNA3 as ready
Hypogonadotropic hypogonadism v0.98 PLXNA3 Chirag Patel Gene: plxna3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 OTX2 Chirag Patel Marked gene: OTX2 as ready
Hypogonadotropic hypogonadism v0.98 OTX2 Chirag Patel Gene: otx2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 NR0B1 Chirag Patel Marked gene: NR0B1 as ready
Hypogonadotropic hypogonadism v0.98 NR0B1 Chirag Patel Gene: nr0b1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 NOS1 Chirag Patel Marked gene: NOS1 as ready
Hypogonadotropic hypogonadism v0.98 NOS1 Chirag Patel Gene: nos1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 LHX4 Chirag Patel Marked gene: LHX4 as ready
Hypogonadotropic hypogonadism v0.98 LHX4 Chirag Patel Gene: lhx4 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 LHX3 Chirag Patel Marked gene: LHX3 as ready
Hypogonadotropic hypogonadism v0.98 LHX3 Chirag Patel Gene: lhx3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 LHB Chirag Patel Marked gene: LHB as ready
Hypogonadotropic hypogonadism v0.98 LHB Chirag Patel Gene: lhb has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 KLB Chirag Patel Marked gene: KLB as ready
Hypogonadotropic hypogonadism v0.98 KLB Chirag Patel Gene: klb has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 KISS1R Chirag Patel Marked gene: KISS1R as ready
Hypogonadotropic hypogonadism v0.98 KISS1R Chirag Patel Gene: kiss1r has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 HID1 Chirag Patel Marked gene: HID1 as ready
Hypogonadotropic hypogonadism v0.98 HID1 Chirag Patel Gene: hid1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 HESX1 Chirag Patel Marked gene: HESX1 as ready
Hypogonadotropic hypogonadism v0.98 HESX1 Chirag Patel Gene: hesx1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GNRHR Chirag Patel Marked gene: GNRHR as ready
Hypogonadotropic hypogonadism v0.98 GNRHR Chirag Patel Gene: gnrhr has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GNRH1 Chirag Patel Marked gene: GNRH1 as ready
Hypogonadotropic hypogonadism v0.98 GNRH1 Chirag Patel Gene: gnrh1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GNAI2 Chirag Patel Marked gene: GNAI2 as ready
Hypogonadotropic hypogonadism v0.98 GNAI2 Chirag Patel Gene: gnai2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GLI3 Chirag Patel Marked gene: GLI3 as ready
Hypogonadotropic hypogonadism v0.98 GLI3 Chirag Patel Gene: gli3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GLI2 Chirag Patel Marked gene: GLI2 as ready
Hypogonadotropic hypogonadism v0.98 GLI2 Chirag Patel Gene: gli2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FSHB Chirag Patel Marked gene: FSHB as ready
Hypogonadotropic hypogonadism v0.98 FSHB Chirag Patel Gene: fshb has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FOXA2 Chirag Patel Marked gene: FOXA2 as ready
Hypogonadotropic hypogonadism v0.98 FOXA2 Chirag Patel Gene: foxa2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FGFR1 Chirag Patel Marked gene: FGFR1 as ready
Hypogonadotropic hypogonadism v0.98 FGFR1 Chirag Patel Gene: fgfr1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FGF8 Chirag Patel Marked gene: FGF8 as ready
Hypogonadotropic hypogonadism v0.98 FGF8 Chirag Patel Gene: fgf8 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FGF17 Chirag Patel Marked gene: FGF17 as ready
Hypogonadotropic hypogonadism v0.98 FGF17 Chirag Patel Gene: fgf17 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 EIF2S3 Chirag Patel Marked gene: EIF2S3 as ready
Hypogonadotropic hypogonadism v0.98 EIF2S3 Chirag Patel Gene: eif2s3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 DCAF17 Chirag Patel Marked gene: DCAF17 as ready
Hypogonadotropic hypogonadism v0.98 DCAF17 Chirag Patel Gene: dcaf17 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 CUL4B Chirag Patel Marked gene: CUL4B as ready
Hypogonadotropic hypogonadism v0.98 CUL4B Chirag Patel Gene: cul4b has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 CHD7 Chirag Patel Marked gene: CHD7 as ready
Hypogonadotropic hypogonadism v0.98 CHD7 Chirag Patel Gene: chd7 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 BMP4 Chirag Patel Marked gene: BMP4 as ready
Hypogonadotropic hypogonadism v0.98 BMP4 Chirag Patel Gene: bmp4 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 ARHGAP35 Chirag Patel Marked gene: ARHGAP35 as ready
Hypogonadotropic hypogonadism v0.98 ARHGAP35 Chirag Patel Gene: arhgap35 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 ANOS1 Chirag Patel Marked gene: ANOS1 as ready
Hypogonadotropic hypogonadism v0.98 ANOS1 Chirag Patel Gene: anos1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.210 SLC40A1 Chirag Patel Classified gene: SLC40A1 as Red List (low evidence)
Monogenic Diabetes v0.210 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.209 SLC40A1 Chirag Patel reviewed gene: SLC40A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Pituitary hormone deficiency v0.195 SLC40A1 Chirag Patel Classified gene: SLC40A1 as Red List (low evidence)
Pituitary hormone deficiency v0.195 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.194 SLC40A1 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Hypogonadotropic hypogonadism v0.98 SLC40A1 Chirag Patel Marked gene: SLC40A1 as ready
Hypogonadotropic hypogonadism v0.98 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.98 SLC40A1 Chirag Patel Classified gene: SLC40A1 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.98 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.97 SLC40A1 Chirag Patel Classified gene: SLC40A1 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.97 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.96 SLC40A1 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Monogenic Diabetes v0.209 HAMP Chirag Patel Classified gene: HAMP as Red List (low evidence)
Monogenic Diabetes v0.209 HAMP Chirag Patel Gene: hamp has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.208 HAMP Chirag Patel reviewed gene: HAMP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hypogonadotropic hypogonadism v0.96 HAMP Chirag Patel Marked gene: HAMP as ready
Hypogonadotropic hypogonadism v0.96 HAMP Chirag Patel Gene: hamp has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.96 HAMP Chirag Patel Classified gene: HAMP as Red List (low evidence)
Hypogonadotropic hypogonadism v0.96 HAMP Chirag Patel Gene: hamp has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.95 HAMP Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.194 HAMP Chirag Patel Classified gene: HAMP as Red List (low evidence)
Pituitary hormone deficiency v0.194 HAMP Chirag Patel Gene: hamp has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.193 HAMP Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Hypogonadotropic hypogonadism v0.95 TFR2 Chirag Patel Marked gene: TFR2 as ready
Hypogonadotropic hypogonadism v0.95 TFR2 Chirag Patel Gene: tfr2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.95 TFR2 Chirag Patel Classified gene: TFR2 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.95 TFR2 Chirag Patel Gene: tfr2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.94 TFR2 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.193 TFR2 Chirag Patel Classified gene: TFR2 as Red List (low evidence)
Pituitary hormone deficiency v0.193 TFR2 Chirag Patel Gene: tfr2 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.192 TFR2 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Monogenic Diabetes v0.208 TFR2 Chirag Patel Classified gene: TFR2 as Red List (low evidence)
Monogenic Diabetes v0.208 TFR2 Chirag Patel Gene: tfr2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.207 TFR2 Chirag Patel reviewed gene: TFR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Pituitary hormone deficiency v0.192 HFE Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Hypogonadotropic hypogonadism v0.94 HFE2 Chirag Patel Marked gene: HFE2 as ready
Hypogonadotropic hypogonadism v0.94 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.94 HFE2 Chirag Patel Classified gene: HFE2 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.94 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.93 HFE2 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.192 HFE2 Chirag Patel Classified gene: HFE2 as Red List (low evidence)
Pituitary hormone deficiency v0.192 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.191 HFE2 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.191 HFE2 Chirag Patel Deleted their comment
Pituitary hormone deficiency v0.191 HFE2 Chirag Patel edited their review of gene: HFE2: Added comment: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.; Changed rating: RED
Pituitary hormone deficiency v0.191 HFE Chirag Patel changed review comment from: Late complication of disease with low lifetime penetrance - not suitable for this panel.; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Hypogonadotropic hypogonadism v0.93 HFE Chirag Patel Marked gene: HFE as ready
Hypogonadotropic hypogonadism v0.93 HFE Chirag Patel Gene: hfe has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.93 HFE Chirag Patel Classified gene: HFE as Red List (low evidence)
Hypogonadotropic hypogonadism v0.93 HFE Chirag Patel Gene: hfe has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.92 HFE Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.191 HFE Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.191 HFE Chirag Patel Classified gene: HFE as Red List (low evidence)
Pituitary hormone deficiency v0.191 HFE Chirag Patel Gene: hfe has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.190 Chirag Patel Added reviews for gene HFE2 from panel Monogenic Diabetes
Hypogonadotropic hypogonadism v0.92 Chirag Patel Added reviews for gene HFE2 from panel Monogenic Diabetes
Monogenic Diabetes v0.207 HFE2 Chirag Patel Classified gene: HFE2 as Red List (low evidence)
Monogenic Diabetes v0.207 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.206 HFE2 Chirag Patel Classified gene: HFE2 as Red List (low evidence)
Monogenic Diabetes v0.206 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.205 HFE2 Chirag Patel reviewed gene: HFE2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Pituitary hormone deficiency v0.189 Chirag Patel Added reviews for gene HFE from panel Monogenic Diabetes
Hypogonadotropic hypogonadism v0.91 Chirag Patel Added reviews for gene HFE from panel Monogenic Diabetes
Monogenic Diabetes v0.205 HFE Chirag Patel Classified gene: HFE as Red List (low evidence)
Monogenic Diabetes v0.205 HFE Chirag Patel Gene: hfe has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.204 HFE Chirag Patel reviewed gene: HFE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital hypothyroidism v0.104 NSD1 Chirag Patel Marked gene: NSD1 as ready
Congenital hypothyroidism v0.104 NSD1 Chirag Patel Gene: nsd1 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.104 NSD1 Chirag Patel Classified gene: NSD1 as Amber List (moderate evidence)
Congenital hypothyroidism v0.104 NSD1 Chirag Patel Gene: nsd1 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.103 NSD1 Chirag Patel gene: NSD1 was added
gene: NSD1 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NSD1 were set to 41024235; 34350334; 15942875
Phenotypes for gene: NSD1 were set to Sotos syndrome, MONDO:0019349
Review for gene: NSD1 was set to AMBER
Added comment: 3 individuals with Sotos syndrome and heterozygous loss‑of‑function NSD1 variants, with permanent congenital hypothyroidism. Congenital hypothyroidism in Sotos syndrome may be an underreported feature.
Sources: Literature
Mendeliome v1.4624 Chirag Patel Added reviews for gene NNT from panel Congenital hypothyroidism
Congenital hypothyroidism v0.102 NNT Chirag Patel changed review comment from: PMID 34545694 describes 3 unrelated families with 3 heterozygous missense NNT variants that produce permanent congenital hypothyroidism due to thyroid dysgenesis. (p.Ala271Ser, p.Arg693His, p.Val861Met). There is no segregation information and the p.Arg693His variant is common in gnomAD. Functional assays (western blot, measurement of NADPH/NADPtotal and H2O2 generation, cell proliferation, and wounding healing assay) showed damaging effect of the NNT variants on stability and catalytic activity of proteins and redox balance of cells, which might lead to the abnormal development of thyroid gland.
Sources: Literature; to: PMID 34545694 describes 3 unrelated families with 3 heterozygous missense NNT variants that produce permanent congenital hypothyroidism due to thyroid agenesis. (p.Ala271Ser, p.Arg693His, p.Val861Met). There is no segregation information and the p.Arg693His variant is common in gnomAD. Functional assays (western blot, measurement of NADPH/NADPtotal and H2O2 generation, cell proliferation, and wounding healing assay) showed damaging effect of the NNT variants on stability and catalytic activity of proteins and redox balance of cells, which might lead to the abnormal development of thyroid gland.
Sources: Literature
Congenital hypothyroidism v0.102 NNT Chirag Patel Marked gene: NNT as ready
Congenital hypothyroidism v0.102 NNT Chirag Patel Gene: nnt has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.102 NNT Chirag Patel gene: NNT was added
gene: NNT was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: NNT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NNT were set to 34545694
Phenotypes for gene: NNT were set to Congenital hypothyroidism, MONDO:0018612
Review for gene: NNT was set to RED
Added comment: PMID 34545694 describes 3 unrelated families with 3 heterozygous missense NNT variants that produce permanent congenital hypothyroidism due to thyroid dysgenesis. (p.Ala271Ser, p.Arg693His, p.Val861Met). There is no segregation information and the p.Arg693His variant is common in gnomAD. Functional assays (western blot, measurement of NADPH/NADPtotal and H2O2 generation, cell proliferation, and wounding healing assay) showed damaging effect of the NNT variants on stability and catalytic activity of proteins and redox balance of cells, which might lead to the abnormal development of thyroid gland.
Sources: Literature
Hand and foot malformations v0.83 Sarah Milton Copied Region IHH upstream regulatory region from panel Mendeliome
Hand and foot malformations v0.83 IHH upstream regulatory region Sarah Milton Region: IHH upstream regulatory region was added
Region: IHH upstream regulatory region was added to Hand and foot malformations. Sources: Literature
Mode of inheritance for Region: IHH upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: IHH upstream regulatory region were set to PMID: 21167467
Phenotypes for Region: IHH upstream regulatory region were set to Craniosynostosis, Philadelphia type, with syndactyly, MIM#185900; Syndactyly, type 1, MIM#185900
Craniosynostosis v1.76 Sarah Milton Copied Region IHH upstream regulatory region from panel Mendeliome
Craniosynostosis v1.76 IHH upstream regulatory region Sarah Milton Region: IHH upstream regulatory region was added
Region: IHH upstream regulatory region was added to Craniosynostosis. Sources: Literature
Mode of inheritance for Region: IHH upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: IHH upstream regulatory region were set to PMID: 21167467
Phenotypes for Region: IHH upstream regulatory region were set to Craniosynostosis, Philadelphia type, with syndactyly, MIM#185900; Syndactyly, type 1, MIM#185900
Mendeliome v1.4623 IHH upstream regulatory region Sarah Milton Region: IHH upstream regulatory region was added
Region: IHH upstream regulatory region was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: IHH upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: IHH upstream regulatory region were set to PMID: 21167467
Phenotypes for Region: IHH upstream regulatory region were set to Craniosynostosis, Philadelphia type, with syndactyly, MIM#185900; Syndactyly, type 1, MIM#185900
Review for Region: IHH upstream regulatory region was set to GREEN
Added comment: IHH belongs to the hedgehog family, and is required for endochondral bone formation by regulating the proliferation and differentiation of chondrocytes. During development IHH is predominantly expressed in prehypertrophic chondrocytes.

PMID: 21167467 describes 3 families with over 80 affected individuals with duplications either including IHH or entirely upstream (in an intron of NHEJ1). These individuals were affected with variable degrees of cutaneous and distal osseus syndactyly and craniosynostosis.

Authors identified duplications in affected families involving conserved non coding elements (either 1 or up to 3 in those with the largest duplications) and cloned an orthologous region into mouse with a fluorescent reporter vector and found staining of chondrocytes indicating this region was a possible enhancer.

Note: OMIM uses coordinates chr2:208,200,001-230,100,000 for this duplication (maximal breakpoints). Minimal region overlap from literature used for Panelapp entry. Further functional studies required to define exact breakpoints.
Sources: Literature
Mendeliome v1.4622 TUBA4A Zornitza Stark Deleted their review
Mendeliome v1.4622 TUBA4A Zornitza Stark Publications for gene: TUBA4A were set to PMID: 38413182
Mendeliome v1.4621 TUBA4A Zornitza Stark Mode of inheritance for gene: TUBA4A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4620 Zornitza Stark Added reviews for gene TUBA4A from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.4619 GBP1 Chirag Patel Marked gene: GBP1 as ready
Mendeliome v1.4619 GBP1 Chirag Patel Gene: gbp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4619 GBP1 Chirag Patel Marked gene: GBP1 as ready
Mendeliome v1.4619 GBP1 Chirag Patel Gene: gbp1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.418 KYNU Chirag Patel Marked gene: KYNU as ready
Skeletal dysplasia v0.418 KYNU Chirag Patel Gene: kynu has been classified as Green List (High Evidence).
Skeletal dysplasia v0.418 KYNU Chirag Patel commented on gene: KYNU
Skeletal dysplasia v0.418 Chirag Patel Copied gene KYNU from panel Mendeliome
Skeletal dysplasia v0.418 KYNU Chirag Patel gene: KYNU was added
gene: KYNU was added to Skeletal dysplasia. Sources: Expert Review Green,NHS GMS,Victorian Clinical Genetics Services
Mode of inheritance for gene: KYNU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KYNU were set to 17334708; 28792876; 31923704
Phenotypes for gene: KYNU were set to Hydroxykynureninuria MIM#236800; Vertebral, cardiac, renal, and limb defects syndrome 2 MIM#617661; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v1.4619 Chirag Patel Copied gene GBP1 from panel Congenital hypothyroidism
Mendeliome v1.4619 GBP1 Chirag Patel gene: GBP1 was added
gene: GBP1 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: GBP1 was set to Unknown
Publications for gene: GBP1 were set to 34194003
Phenotypes for gene: GBP1 were set to Congenital hypothyroidism, MONDO:0018612
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Marked gene: GBP1 as ready
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Gene: gbp1 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.101 GBP1 Chirag Patel reviewed gene: GBP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34194003; Phenotypes: Congenital hypothyroidism, MONDO:0018612; Mode of inheritance: Unknown
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Deleted their review
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Deleted their comment
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Mode of inheritance for gene: GBP1 was changed from BIALLELIC, autosomal or pseudoautosomal to Unknown
Congenital hypothyroidism v0.100 GBP1 Chirag Patel Classified gene: GBP1 as Amber List (moderate evidence)
Congenital hypothyroidism v0.100 GBP1 Chirag Patel Gene: gbp1 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.99 GBP1 Chirag Patel gene: GBP1 was added
gene: GBP1 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: GBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBP1 were set to 34194003
Phenotypes for gene: GBP1 were set to Congenital hypothyroidism, MONDO:0018612
Review for gene: GBP1 was set to AMBER
Added comment: PMID 34194003 reports 3 individuals from 3 unrelated families presenting with congenital hypothyroidism (neonatal onset, elevated TSH, low thyroid hormone, thyroid dysgenesis or diffuse hypoechoic thyroid). 1 individual had biallelic variants (p.E336fs and p.H150Y1) with parents as heterozygous unaffected carriers. The other 2 individuals had a heterozygous variant (p.R20X or p.L187P) inherited from an unaffected parent. Methylation-specific PCR and pyrosequencing found the CpG site of GBP1 was hypermethylated in the genomic DNA isolated from the 2 probands compared with their euthyroid parents.

Zebrafish morpholino knockdown of gbp1 causes thyroid primordium malformation and hypothyroidism. The phenotype was rescued by wild‑type human GBP1 mRNA but not by mutant p.H150Y or p.L187P. Human TPC1 thyroid cells expressing mutant GBP1 show mislocalisation, loss of β‑catenin interaction and disrupted adhesion complex formation.
Sources: Literature
Congenital hypothyroidism v0.98 FOXP3 Chirag Patel Marked gene: FOXP3 as ready
Congenital hypothyroidism v0.98 FOXP3 Chirag Patel Gene: foxp3 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.98 FOXP3 Chirag Patel Classified gene: FOXP3 as Amber List (moderate evidence)
Congenital hypothyroidism v0.98 FOXP3 Chirag Patel Gene: foxp3 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.97 FOXP3 Chirag Patel reviewed gene: FOXP3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital hypothyroidism v0.97 Chirag Patel Copied gene FOXP3 from panel Mendeliome
Congenital hypothyroidism v0.97 FOXP3 Chirag Patel gene: FOXP3 was added
gene: FOXP3 was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
treatable tags were added to gene: FOXP3.
Mode of inheritance for gene: FOXP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FOXP3 were set to 11295725; 11137993; 33668198; 33614561; 33330291; 32234571
Phenotypes for gene: FOXP3 were set to Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790
Ataxia v1.197 DNAJC3 Chirag Patel Marked gene: DNAJC3 as ready
Ataxia v1.197 DNAJC3 Chirag Patel Gene: dnajc3 has been classified as Green List (High Evidence).
Ataxia v1.197 Chirag Patel Copied gene DNAJC3 from panel Congenital hypothyroidism
Ataxia v1.197 DNAJC3 Chirag Patel gene: DNAJC3 was added
gene: DNAJC3 was added to Ataxia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 34654017; 34630333; 33486469; 32738013; 28940199
Phenotypes for gene: DNAJC3 were set to juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome, MONDO:0014523
Congenital hypothyroidism v0.96 DNAJC3 Chirag Patel Marked gene: DNAJC3 as ready
Congenital hypothyroidism v0.96 DNAJC3 Chirag Patel Gene: dnajc3 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.96 DNAJC3 Chirag Patel Classified gene: DNAJC3 as Green List (high evidence)
Congenital hypothyroidism v0.96 DNAJC3 Chirag Patel Gene: dnajc3 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.95 DNAJC3 Chirag Patel gene: DNAJC3 was added
gene: DNAJC3 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 34654017; 34630333; 33486469; 32738013; 28940199
Phenotypes for gene: DNAJC3 were set to juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome, MONDO:0014523
Review for gene: DNAJC3 was set to GREEN
Added comment: 14 individuals from 8 unrelated families with biallelic variants in DNAJC3, presenting with congenital/early‑onset hypothyroidism, early‑onset diabetes mellitus, neuropathy, cerebellar ataxia, progressive neurodegeneration, short stature, and sensorineural hearing loss.
Sources: Literature
Mendeliome v1.4618 LSM7 Sangavi Sivagnanasundram edited their review of gene: LSM7: Added comment: Addition of publication - GDA remain as AMBER as no new evidence as been reported; Changed publications: 39420558, 35047835; Changed phenotypes: Neurodevelopmental disorder with leukodystrophy and cerebellar atrophy MONDO:0700092
Hypogonadotropic hypogonadism v0.90 CPE Chirag Patel Phenotypes for gene: CPE were changed from Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326 to BDV syndrome MONDO:0859150
Hypogonadotropic hypogonadism v0.89 CPE Chirag Patel Marked gene: CPE as ready
Hypogonadotropic hypogonadism v0.89 CPE Chirag Patel Gene: cpe has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.89 Chirag Patel Added reviews for gene CPE from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.188 CPE Chirag Patel Publications for gene: CPE were set to 26120850; 32936766; 34383079
Pituitary hormone deficiency v0.187 CPE Chirag Patel Phenotypes for gene: CPE were changed from Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326 to BDV syndrome MONDO:0859150
Pituitary hormone deficiency v0.186 CPE Chirag Patel Marked gene: CPE as ready
Pituitary hormone deficiency v0.186 CPE Chirag Patel Gene: cpe has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.186 CPE Chirag Patel reviewed gene: CPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 34383079, 26120850,32936766; Phenotypes: BDV syndrome MONDO:0859150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v1.196 RAB3A Zornitza Stark Phenotypes for gene: RAB3A were changed from autosomal dominant cerebellar ataxia MONDO:0020380 to Spinocerebellar ataxia 52, MIM# 621535
Ataxia v1.195 RAB3A Zornitza Stark reviewed gene: RAB3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 52, MIM# 621535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4618 RAB3A Zornitza Stark Phenotypes for gene: RAB3A were changed from autosomal dominant cerebellar ataxia MONDO:0020380; neurodevelopmental disorder MONDO:0700092 to Spinocerebellar ataxia 52, MIM# 621535; neurodevelopmental disorder MONDO:0700092
Pituitary hormone deficiency v0.186 Chirag Patel Copied gene CPE from panel Mendeliome
Pituitary hormone deficiency v0.186 CPE Chirag Patel gene: CPE was added
gene: CPE was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPE were set to 26120850; 32936766; 34383079
Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Hypogonadotropic hypogonadism v0.88 Chirag Patel Copied gene CPE from panel Mendeliome
Hypogonadotropic hypogonadism v0.88 CPE Chirag Patel gene: CPE was added
gene: CPE was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPE were set to 26120850; 32936766; 34383079
Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Mendeliome v1.4617 RAB3A Zornitza Stark reviewed gene: RAB3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 52, MIM# 621535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital hypothyroidism v0.94 CDC42 Chirag Patel Publications for gene: CDC42 were set to 30872706; 29335451
Congenital hypothyroidism v0.93 CDC42 Chirag Patel Marked gene: CDC42 as ready
Congenital hypothyroidism v0.93 CDC42 Chirag Patel Gene: cdc42 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.93 CDC42 Chirag Patel Classified gene: CDC42 as Amber List (moderate evidence)
Congenital hypothyroidism v0.93 CDC42 Chirag Patel Gene: cdc42 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.92 CDC42 Chirag Patel gene: CDC42 was added
gene: CDC42 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: CDC42 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42 were set to 30872706; 29335451
Phenotypes for gene: CDC42 were set to Congenital hypothyroidism, MONDO:0018612
Review for gene: CDC42 was set to AMBER
Added comment: ClinGen DEFINITIVE for Takenouchi-Kosaki syndrome (Oct 2021).

3 individuals with Takenouchi-Kosaki syndrome and congenital hypothyroidism. They all had the same rare de novo missense variant in CDC42 (p.Tyr64Cys). C. elegans knock‑in model demonstrated a hypomorphic loss‑of‑function effect. (NB 1 overlapping family between PMID 29335451 and PMID 30872706)
Sources: Literature
Congenital hypothyroidism v0.91 DUOX1 Chirag Patel edited their review of gene: DUOX1: Added comment: PMID 31428054:
1 individual with congenital hypothyroidism with heterozygous missense variant in DUOX1 (p.R1307Q). No segregation testing and variant is too common in gnomAD. HeLa cell overexpression of the p.R1307Q mutant showed reduced DUOX1 mRNA, protein and H₂O₂ production.

PMID 27373559:
1 individual with congenital hypothyroidism with heterozygous missense variant in DUOX1 (p.P219L). No segregation testing and no functional testing, and variant is too common in gnomAD.

PMID 33631011:
14 individuals with congenital hypothyroidism with DUOX1 variants (13 missense, 1 nonsense), BUT no information on individual phenotypes, segregation data, or functional validation.; Changed rating: RED; Changed publications: 31428054, 27373559, 33631011:; Changed phenotypes: Congenital hypothyroidism, MONDO:0018612; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.712 TRIM71 Zornitza Stark Marked gene: TRIM71 as ready
Intellectual disability syndromic and non-syndromic v1.712 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.712 TRIM71 Zornitza Stark Publications for gene: TRIM71 were set to 29983323; 32168371; 30975633; 40892928
Intellectual disability syndromic and non-syndromic v1.711 TRIM71 Zornitza Stark edited their review of gene: TRIM71: Added comment: PMID 38833623 reports 20 individuals from 13 unrelated families with heterozygous de novo or rare inherited TRIM71 variants (missense, nonsense, splice‑site, frameshift) presenting with congenital hydrocephalus/ventriculomegaly, developmental delay, dysmorphic features, corpus callosum dysgenesis, white‑matter hypoplasia, limb and craniofacial anomalies, hearing and cardiac defects. Functional studies in HEK293T cells show NHL‑domain missense variants impair binding to CDKN1A/EGR1 and disrupt P‑body localization, supporting loss‑of‑function/altered‑function mechanisms.; Changed publications: 40892928, 38833623
Intellectual disability syndromic and non-syndromic v1.711 Zornitza Stark Copied gene TRIM71 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.711 TRIM71 Zornitza Stark gene: TRIM71 was added
gene: TRIM71 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIM71 were set to 29983323; 32168371; 30975633; 40892928
Phenotypes for gene: TRIM71 were set to Congenital hydrocephalus 4 (MIM#618667)
Mendeliome v1.4617 TRIM71 Zornitza Stark Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633
Mendeliome v1.4616 TRIM71 Zornitza Stark changed review comment from: Reports 3 individuals from 3 unrelated families with heterozygous missense TRIM71 variants (p.Q334R, p.R608H, p.R796H) presenting with childhood‑onset syndromic hearing loss, often accompanied by congenital hydrocephalus, renal cysts, facial dysmorphism and other developmental anomalies. Two individuals (p.Q334R and p.R608H) have detailed clinical work‑up (sensorineural or mixed severe loss, inner ear malformations) and functional assays demonstrate that p.Q334R mis‑localises TRIM71 to P‑bodies and p.R608H disrupts RNA binding. Mouse models with loss‑of‑function or the human HL‑associated missense allele recapitulate severe hearing loss, confirming the pathogenic mechanism as loss‑of‑function of TRIM71.; to: Reports 3 individuals from 3 unrelated families with heterozygous missense TRIM71 variants (p.Q334R, p.R608H, p.R796H) presenting with childhood‑onset syndromic hearing loss, often accompanied by congenital hydrocephalus, renal cysts, facial dysmorphism and other developmental anomalies. Two individuals (p.Q334R and p.R608H) have detailed clinical work‑up (sensorineural or mixed severe loss, inner ear malformations) and functional assays demonstrate that p.Q334R mis‑localises TRIM71 to P‑bodies and p.R608H disrupts RNA binding. Mouse models with loss‑of‑function or the human HL‑associated missense allele recapitulate severe hearing loss, confirming the pathogenic mechanism as loss‑of‑function of TRIM71.

Likely phenotype expansion.
Mendeliome v1.4616 TRIM71 Zornitza Stark reviewed gene: TRIM71: Rating: GREEN; Mode of pathogenicity: None; Publications: 40892928; Phenotypes: Congenital hydrocephalus 4 (MIM#618667); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.340 TRIM71 Zornitza Stark Marked gene: TRIM71 as ready
Deafness_IsolatedAndComplex v1.340 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.340 TRIM71 Zornitza Stark Classified gene: TRIM71 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.340 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.339 TRIM71 Zornitza Stark gene: TRIM71 was added
gene: TRIM71 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM71 were set to 40892928
Phenotypes for gene: TRIM71 were set to Congenital hydrocephalus 4 (MIM#618667)
Review for gene: TRIM71 was set to GREEN
Added comment: Reports 3 individuals from 3 unrelated families with heterozygous missense TRIM71 variants (p.Q334R, p.R608H, p.R796H) presenting with childhood‑onset syndromic hearing loss, often accompanied by congenital hydrocephalus, renal cysts, facial dysmorphism and other developmental anomalies. Two individuals (p.Q334R and p.R608H) have detailed clinical work‑up (sensorineural or mixed severe loss, inner ear malformations) and functional assays demonstrate that p.Q334R mis‑localises TRIM71 to P‑bodies and p.R608H disrupts RNA binding. Mouse models with loss‑of‑function or the human HL‑associated missense allele recapitulate severe hearing loss, confirming the pathogenic mechanism as loss‑of‑function of TRIM71.
Sources: Literature
Mendeliome v1.4616 TNFRSF11A Zornitza Stark Phenotypes for gene: TNFRSF11A were changed from Osteopetrosis, autosomal recessive 7 - MIM# 612301 to Osteopetrosis, autosomal recessive 7 - MIM# 612301; familial expansile osteolysis, MONDO:0008275
Mendeliome v1.4615 TNFRSF11A Zornitza Stark Publications for gene: TNFRSF11A were set to 18606301; 32048120
Mendeliome v1.4614 TNFRSF11A Zornitza Stark Mode of inheritance for gene: TNFRSF11A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4613 TNFRSF11A Zornitza Stark edited their review of gene: TNFRSF11A: Added comment: Two independent studies (PMID 36740137, PMID 40222603) document three unrelated families with heterozygous exon‑1 in‑frame duplications (c.52_63dup, c.39_65dup) that act as gain‑of‑function alleles, producing a dominant dento‑osseous / familial expansile osteolysis phenotype with hearing loss, tooth root resorption and tendon avulsion.; Changed publications: 10.64898/2026.02.18.706528, 40222603, 36740137, 35812760, 33037392, 31163101; Changed phenotypes: familial expansile osteolysis, MONDO:0008275; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.35 TBK1 Zornitza Stark Marked gene: TBK1 as ready
Defects of intrinsic and innate immunity v1.35 TBK1 Zornitza Stark Gene: tbk1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.35 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from to Hereditary predisposition to infections, MONDO:0015979, TBK1-related
Defects of intrinsic and innate immunity v1.34 TBK1 Zornitza Stark Publications for gene: TBK1 were set to
Defects of intrinsic and innate immunity v1.33 TBK1 Zornitza Stark Mode of inheritance for gene: TBK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v1.22 POLD1 Zornitza Stark Marked gene: POLD1 as ready
Mandibulofacial Acrofacial dysostosis v1.22 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v1.22 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Immunodeficiency 120, MIM# 620836 to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381
Mandibulofacial Acrofacial dysostosis v1.21 POLD1 Zornitza Stark Mode of inheritance for gene: POLD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v1.20 POLD1 Zornitza Stark Deleted their comment
Mandibulofacial Acrofacial dysostosis v1.20 POLD1 Zornitza Stark edited their review of gene: POLD1: Changed phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v1.20 Zornitza Stark Copied gene POLD1 from panel Mendeliome
Mandibulofacial Acrofacial dysostosis v1.20 POLD1 Zornitza Stark gene: POLD1 was added
gene: POLD1 was added to Mandibulofacial Acrofacial dysostosis. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POLD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLD1 were set to 31629014; 31449058; 23770608; 33618333; 33369179; 32826474; 30023403; 29199204; 28791128
Phenotypes for gene: POLD1 were set to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Immunodeficiency 120, MIM# 620836
Incidentalome v0.433 OPTN Zornitza Stark Marked gene: OPTN as ready
Incidentalome v0.433 OPTN Zornitza Stark Gene: optn has been classified as Green List (High Evidence).
Incidentalome v0.433 OPTN Zornitza Stark Phenotypes for gene: OPTN were changed from to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MONDO: 0013264, MIM#613435)
Incidentalome v0.432 OPTN Zornitza Stark Publications for gene: OPTN were set to
Incidentalome v0.431 OPTN Zornitza Stark Mode of inheritance for gene: OPTN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.545 NUS1 Zornitza Stark Classified gene: NUS1 as Red List (low evidence)
Fetal anomalies v1.545 NUS1 Zornitza Stark Gene: nus1 has been classified as Red List (Low Evidence).
Fetal anomalies v1.544 NUS1 Zornitza Stark edited their review of gene: NUS1: Added comment: Limited evidence for the AR disorder, little if any replication over time which is concerning. Monoallelic disorder lacks prenatal findings.; Changed rating: RED
Mendeliome v1.4613 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Congenital disorder of glycosylation, type 1aa 617082; Mental retardation, autosomal dominant 55, with seizures 617831 to Intellectual developmental disorder, autosomal dominant 55, with seizures, MIM# 617831
Mendeliome v1.4612 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4611 NUS1 Zornitza Stark reviewed gene: NUS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 1aa, MIM# 617082; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.84 NUS1 Zornitza Stark Classified gene: NUS1 as Red List (low evidence)
Congenital Disorders of Glycosylation v1.84 NUS1 Zornitza Stark Gene: nus1 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v1.83 NUS1 Zornitza Stark reviewed gene: NUS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 1aa, MIM# 617082; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.76 KNG1 Zornitza Stark Marked gene: KNG1 as ready
Bleeding and Platelet Disorders v1.76 KNG1 Zornitza Stark Gene: kng1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.76 KNG1 Zornitza Stark Phenotypes for gene: KNG1 were changed from angioedema, hereditary, 6, MONDO:0023660; congenital high-molecular-weight kininogen deficiency, MONDO:0009234 to congenital high-molecular-weight kininogen deficiency, MONDO:0009234
Bleeding and Platelet Disorders v1.75 KNG1 Zornitza Stark Publications for gene: KNG1 were set to 41634406; 40848077; 36700498; 33114181; 32185598; 31858768; 31087670
Bleeding and Platelet Disorders v1.74 KNG1 Zornitza Stark Mode of inheritance for gene: KNG1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.73 KNG1 Zornitza Stark Deleted their comment
Bleeding and Platelet Disorders v1.73 KNG1 Zornitza Stark Deleted their comment
Bleeding and Platelet Disorders v1.73 KNG1 Zornitza Stark edited their review of gene: KNG1: Changed publications: 36700498; Changed phenotypes: congenital high-molecular-weight kininogen deficiency, MONDO:0009234; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.73 Zornitza Stark Copied gene KNG1 from panel Mendeliome
Bleeding and Platelet Disorders v1.73 KNG1 Zornitza Stark gene: KNG1 was added
gene: KNG1 was added to Bleeding and Platelet Disorders. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KNG1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KNG1 were set to 41634406; 40848077; 36700498; 33114181; 32185598; 31858768; 31087670
Phenotypes for gene: KNG1 were set to angioedema, hereditary, 6, MONDO:0023660; congenital high-molecular-weight kininogen deficiency, MONDO:0009234
Mendeliome v1.4611 KNG1 Zornitza Stark Phenotypes for gene: KNG1 were changed from Hereditary angioedema-6 (HAE6), MIM#619363 to angioedema, hereditary, 6, MONDO:0023660; congenital high-molecular-weight kininogen deficiency, MONDO:0009234
Mendeliome v1.4610 KNG1 Zornitza Stark Publications for gene: KNG1 were set to 31087670; 33114181
Mendeliome v1.4609 KNG1 Zornitza Stark Mode of inheritance for gene: KNG1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4608 KNG1 Zornitza Stark edited their review of gene: KNG1: Added comment: PMID 36700498 aggregates 48 patients from 41 unrelated families with biallelic truncating or splice‑site KNG1 variants. Prolonged aPTT and but lack of evidence for increased incidence of major bleeding episodes.; Changed publications: 41634406, 40848077, 36700498, 33114181, 32185598, 31858768, 31087670; Changed phenotypes: angioedema, hereditary, 6, MONDO:0023660, congenital high-molecular-weight kininogen deficiency, MONDO:0009234; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Desmosomal disorders v1.4 WNT10A Zornitza Stark Marked gene: WNT10A as ready
Desmosomal disorders v1.4 WNT10A Zornitza Stark Gene: wnt10a has been classified as Red List (Low Evidence).
Desmosomal disorders v1.4 WNT10A Zornitza Stark Phenotypes for gene: WNT10A were changed from to Odontoonychodermal dysplasia 257980 AR Schopf-Schulz-Passarge syndrome 224750 AR Tooth agenesis, selective, 4 150400 AR, AD
Desmosomal disorders v1.3 WNT10A Zornitza Stark Mode of inheritance for gene: WNT10A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Desmosomal disorders v1.2 WNT10A Zornitza Stark Publications for gene: WNT10A were set to
Desmosomal disorders v1.1 WNT10A Zornitza Stark Classified gene: WNT10A as Red List (low evidence)
Desmosomal disorders v1.1 WNT10A Zornitza Stark Gene: wnt10a has been classified as Red List (Low Evidence).
Desmosomal disorders v1.0 WNT10A Zornitza Stark reviewed gene: WNT10A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Desmosomal disorders v1.0 Zornitza Stark promoted panel to version 1.0
Desmosomal disorders v0.40 DSG3 Zornitza Stark Marked gene: DSG3 as ready
Desmosomal disorders v0.40 DSG3 Zornitza Stark Gene: dsg3 has been classified as Amber List (Moderate Evidence).
Desmosomal disorders v0.40 Zornitza Stark Copied gene DSG3 from panel Epidermolysis bullosa
Desmosomal disorders v0.40 DSG3 Zornitza Stark gene: DSG3 was added
gene: DSG3 was added to Desmosomal disorders. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: DSG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSG3 were set to 26763450; 37850634; 30528827
Phenotypes for gene: DSG3 were set to Blistering, acantholytic, of oral and laryngeal mucosa, MIM# 619226
Desmosomal disorders v0.39 TP63 Zornitza Stark Marked gene: TP63 as ready
Desmosomal disorders v0.39 TP63 Zornitza Stark Gene: tp63 has been classified as Green List (High Evidence).
Desmosomal disorders v0.39 TP63 Zornitza Stark Phenotypes for gene: TP63 were changed from to Rapp-Hodgkin syndrome, MIM# 129400
Desmosomal disorders v0.38 TP63 Zornitza Stark Mode of inheritance for gene: TP63 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Desmosomal disorders v0.37 TP63 Zornitza Stark reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rapp-Hodgkin syndrome, MIM# 129400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Desmosomal disorders v0.37 EDARADD Zornitza Stark Marked gene: EDARADD as ready
Desmosomal disorders v0.37 EDARADD Zornitza Stark Gene: edaradd has been classified as Green List (High Evidence).
Desmosomal disorders v0.37 DSP Zornitza Stark Marked gene: DSP as ready
Desmosomal disorders v0.37 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Desmosomal disorders v0.37 DSP Zornitza Stark Phenotypes for gene: DSP were changed from to Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821
Desmosomal disorders v0.36 DSP Zornitza Stark Mode of inheritance for gene: DSP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Desmosomal disorders v0.35 DSP Zornitza Stark reviewed gene: DSP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Corneal Dystrophy v1.21 TUBA3D Zornitza Stark Marked gene: TUBA3D as ready
Corneal Dystrophy v1.21 TUBA3D Zornitza Stark Gene: tuba3d has been classified as Amber List (Moderate Evidence).
Central Hypoventilation v1.7 PHOX2B_CCHS_GCN Zornitza Stark Marked STR: PHOX2B_CCHS_GCN as ready
Central Hypoventilation v1.7 PHOX2B_CCHS_GCN Zornitza Stark Str: phox2b_cchs_gcn has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v1.0 Zornitza Stark promoted panel to version 1.0
Cataract v1.0 Zornitza Stark promoted panel to version 1.0
Cataract v0.631 ELP4 Zornitza Stark Marked gene: ELP4 as ready
Cataract v0.631 ELP4 Zornitza Stark Gene: elp4 has been classified as Green List (High Evidence).
Cataract v0.631 CRYBA2 Zornitza Stark Marked gene: CRYBA2 as ready
Cataract v0.631 CRYBA2 Zornitza Stark Gene: cryba2 has been classified as Green List (High Evidence).
Autonomic neuropathy v1.2 Zornitza Stark HPO terms changed from Abnormality of the autonomic nervous system HP:0002270 to
List of related panels changed from to Abnormality of the autonomic nervous system HP:0002270
Autonomic neuropathy v1.1 Zornitza Stark HPO terms changed from to Abnormality of the autonomic nervous system HP:0002270
Autonomic neuropathy v1.0 Zornitza Stark promoted panel to version 1.0
Autonomic neuropathy v0.51 NGF Zornitza Stark Marked gene: NGF as ready
Autonomic neuropathy v0.51 NGF Zornitza Stark Gene: ngf has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v1.0 Zornitza Stark promoted panel to version 1.0
Atypical Haemolytic Uraemic Syndrome_MPGN v0.68 DGKE Zornitza Stark Marked gene: DGKE as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.68 DGKE Zornitza Stark Gene: dgke has been classified as Red List (Low Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.68 DGKE Zornitza Stark Phenotypes for gene: DGKE were changed from to Nephrotic syndrome, type 7, MIM# 615008
Atypical Haemolytic Uraemic Syndrome_MPGN v0.67 DGKE Zornitza Stark Publications for gene: DGKE were set to
Atypical Haemolytic Uraemic Syndrome_MPGN v0.66 DGKE Zornitza Stark Mode of inheritance for gene: DGKE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Atypical Haemolytic Uraemic Syndrome_MPGN v0.65 DGKE Zornitza Stark Classified gene: DGKE as Red List (low evidence)
Atypical Haemolytic Uraemic Syndrome_MPGN v0.65 DGKE Zornitza Stark Gene: dgke has been classified as Red List (Low Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.64 DGKE Zornitza Stark edited their review of gene: DGKE: Added comment: Not appropriate for this panel, causes nephrotic syndrome.; Changed rating: RED
Atypical Haemolytic Uraemic Syndrome_MPGN v0.64 CFI Zornitza Stark Marked gene: CFI as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.64 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.64 CFI Zornitza Stark Phenotypes for gene: CFI were changed from to {Haemolytic uremic syndrome, atypical, susceptibility to, 3} MIM#612923
Atypical Haemolytic Uraemic Syndrome_MPGN v0.63 CFI Zornitza Stark Publications for gene: CFI were set to
Atypical Haemolytic Uraemic Syndrome_MPGN v0.62 CFI Zornitza Stark Mode of inheritance for gene: CFI was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Atypical Haemolytic Uraemic Syndrome_MPGN v0.61 CFHR5 Zornitza Stark Marked gene: CFHR5 as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.61 CFHR5 Zornitza Stark Gene: cfhr5 has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.61 CFHR5 Zornitza Stark Phenotypes for gene: CFHR5 were changed from to Nephropathy due to CFHR5 deficiency, MIM#614809
Atypical Haemolytic Uraemic Syndrome_MPGN v0.60 CFHR5 Zornitza Stark Publications for gene: CFHR5 were set to
Atypical Haemolytic Uraemic Syndrome_MPGN v0.59 CFHR5 Zornitza Stark Mode of inheritance for gene: CFHR5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atypical Haemolytic Uraemic Syndrome_MPGN v0.58 CFH Zornitza Stark Marked gene: CFH as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.58 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.58 CFH Zornitza Stark Phenotypes for gene: CFH were changed from to {Haemolytic uremic syndrome, atypical, susceptibility to, 1} MIMI#235400
Atypical Haemolytic Uraemic Syndrome_MPGN v0.57 CFH Zornitza Stark Publications for gene: CFH were set to
Atypical Haemolytic Uraemic Syndrome_MPGN v0.56 CFH Zornitza Stark Mode of inheritance for gene: CFH was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Arrhythmogenic Cardiomyopathy v1.0 Zornitza Stark promoted panel to version 1.0
Arrhythmogenic Cardiomyopathy v0.78 CTNNA3 Zornitza Stark Marked gene: CTNNA3 as ready
Arrhythmogenic Cardiomyopathy v0.78 CTNNA3 Zornitza Stark Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v1.0 Zornitza Stark promoted panel to version 1.0
Renal Macrocystic Disease v1.0 Chirag Patel promoted panel to version 1.0
Renal Macrocystic Disease v0.112 CFAP47 Zornitza Stark Marked gene: CFAP47 as ready
Renal Macrocystic Disease v0.112 CFAP47 Zornitza Stark Gene: cfap47 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.112 CFAP47 Zornitza Stark Classified gene: CFAP47 as Red List (low evidence)
Renal Macrocystic Disease v0.112 CFAP47 Zornitza Stark Gene: cfap47 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.111 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Renal Macrocystic Disease v0.111 TSC2 Zornitza Stark Gene: tsc2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.111 TSC2 Zornitza Stark Phenotypes for gene: TSC2 were changed from to Tuberous sclerosis-2, MIM# 613254
Renal Macrocystic Disease v0.110 TSC2 Zornitza Stark Mode of inheritance for gene: TSC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.109 ISCA-37432-Loss Zornitza Stark Marked Region: ISCA-37432-Loss as ready
Renal Macrocystic Disease v0.109 ISCA-37432-Loss Zornitza Stark Region: isca-37432-loss has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.109 CYS1 Zornitza Stark Marked gene: CYS1 as ready
Renal Macrocystic Disease v0.109 CYS1 Zornitza Stark Gene: cys1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.109 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Renal Macrocystic Disease v0.109 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.109 TSC1 Zornitza Stark Phenotypes for gene: TSC1 were changed from to Tuberous sclerosis-1, MIM#191100
Renal Macrocystic Disease v0.108 TSC1 Zornitza Stark Publications for gene: TSC1 were set to
Renal Macrocystic Disease v0.107 TSC1 Zornitza Stark Mode of inheritance for gene: TSC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v1.19 FOXI3 Zornitza Stark Phenotypes for gene: FOXI3 were changed from Dysostosis with predominant craniofacial involvement (MONDO:0800085) to Craniofacial microsomia 2, MIM# 620444
Mandibulofacial Acrofacial dysostosis v1.18 FOXI3 Zornitza Stark Publications for gene: FOXI3 were set to 36260083
Mandibulofacial Acrofacial dysostosis v1.17 FOXI3 Zornitza Stark reviewed gene: FOXI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37041148; Phenotypes: Craniofacial microsomia 2, MIM# 620444; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4608 FOXI3 Zornitza Stark Phenotypes for gene: FOXI3 were changed from Dysostosis with predominant craniofacial involvement (MONDO:0800085) to Craniofacial microsomia 2, MIM# 620444
Mendeliome v1.4607 FOXI3 Zornitza Stark Publications for gene: FOXI3 were set to 36260083
Mendeliome v1.4606 FOXI3 Zornitza Stark reviewed gene: FOXI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37041148; Phenotypes: Craniofacial microsomia 2, MIM# 620444; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v1.44 MARS2 Elena Tucker reviewed gene: MARS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cardiomyopathy_Paediatric v0.225 ALMS1 Chirag Patel Phenotypes for gene: ALMS1 were changed from OMIM 203800 to Cardiomyopathy, MONDO:0004994
Dilated Cardiomyopathy v1.63 ALMS1 Chirag Patel Marked gene: ALMS1 as ready
Dilated Cardiomyopathy v1.63 ALMS1 Chirag Patel Gene: alms1 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.63 ALMS1 Chirag Patel Phenotypes for gene: ALMS1 were changed from OMIM 203800 to Cardiomyopathy, MONDO:0004994
Dilated Cardiomyopathy v1.62 Chirag Patel Copied gene ALMS1 from panel Cardiomyopathy_Paediatric
Dilated Cardiomyopathy v1.62 ALMS1 Chirag Patel gene: ALMS1 was added
gene: ALMS1 was added to Dilated Cardiomyopathy. Sources: Expert Review Green,Expert Review,NHS GMS
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALMS1 were set to 15689433
Phenotypes for gene: ALMS1 were set to OMIM 203800
Cardiomyopathy_Paediatric v0.224 ALMS1 Chirag Patel Marked gene: ALMS1 as ready
Cardiomyopathy_Paediatric v0.224 ALMS1 Chirag Patel Gene: alms1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.224 ALMS1 Chirag Patel reviewed gene: ALMS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, MONDO:0004994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.710 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to Ebstein-Bezieau neurodevelopmental syndrome, MIM# 621539; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v1.4606 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to Ebstein-Bezieau neurodevelopmental syndrome, MIM# 621539; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v1.4605 PSMC3 Zornitza Stark edited their review of gene: PSMC3: Changed phenotypes: Ebstein-Bezieau neurodevelopmental syndrome, MIM# 621539, Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Deafness_IsolatedAndComplex v1.338 CLRN2 Bryony Thompson Publications for gene: CLRN2 were set to 33496845
Deafness_IsolatedAndComplex v1.337 CLRN2 Bryony Thompson Classified gene: CLRN2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.337 CLRN2 Bryony Thompson Gene: clrn2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.336 Bryony Thompson Added reviews for gene CLRN2 from panel Mendeliome
Mendeliome v1.4605 CLRN2 Bryony Thompson Publications for gene: CLRN2 were set to 33496845
Mendeliome v1.4604 CLRN2 Bryony Thompson Classified gene: CLRN2 as Green List (high evidence)
Mendeliome v1.4604 CLRN2 Bryony Thompson Gene: clrn2 has been classified as Green List (High Evidence).
Mendeliome v1.4603 CLRN2 Bryony Thompson reviewed gene: CLRN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39446282, 38243601, 33496845; Phenotypes: hearing loss, autosomal recessive 117, MONDO:0030905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.133 Bryony Thompson Copied gene CEP112 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.133 CEP112 Bryony Thompson gene: CEP112 was added
gene: CEP112 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP112 were set to 39349455; 31654588
Phenotypes for gene: CEP112 were set to Spermatogenic failure 44, MIM#619044; Acephalic spermatozoa; infertility
Mendeliome v1.4603 CEP112 Bryony Thompson Publications for gene: CEP112 were set to 31654588
Mendeliome v1.4602 CEP112 Bryony Thompson Deleted their comment
Mendeliome v1.4602 CEP112 Bryony Thompson edited their review of gene: CEP112: Added comment: PMIDs 31654588, 39349455 report a total of 4 unrelated families (4patients) with biallelic loss‑of‑function CEP112 variants causing male infertility phenotypes ranging from acephalic spermatozoa to oligoasthenoteratozoospermia and non‑obstructive azoospermia. Functional evidence includes loss of CEP112 protein in patient sperm, mouse Cep112 knockout infertility with ICSI rescue, and impaired phase‑separation of mutant proteins, supporting a diagnostic‑grade association of CEP112 with spermatogenic failure 44.; Changed publications: 39349455, 31654588; Changed phenotypes: spermatogenic failure 44, MONDO:0033622
Mendeliome v1.4602 CEP112 Bryony Thompson Classified gene: CEP112 as Green List (high evidence)
Mendeliome v1.4602 CEP112 Bryony Thompson Gene: cep112 has been classified as Green List (High Evidence).
Mendeliome v1.4601 CEP112 Bryony Thompson edited their review of gene: CEP112: Added comment: Now 4 unrelated biallelic male cases and a supporting mouse model.; Changed rating: GREEN; Changed publications: 31654588, 39349455; Changed phenotypes: spermatogenic failure MONDO:0004983
Mendeliome v1.4601 SLC30A5 Lucy Spencer reviewed gene: SLC30A5: Rating: AMBER; Mode of pathogenicity: None; Publications: 39790720; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4601 RUSC2 Lucy Spencer Phenotypes for gene: RUSC2 were changed from Mental retardation, autosomal recessive 61, MIM# 617773 to Intellectual developmental disorder, autosomal recessive 61 MIM#617773
Mendeliome v1.4600 RUSC2 Lucy Spencer Publications for gene: RUSC2 were set to 27612186
Mendeliome v1.4599 RUSC2 Lucy Spencer reviewed gene: RUSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 36553572, 27612186; Phenotypes: Intellectual developmental disorder, autosomal recessive 61 MIM#617773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Movement Disorders Superpanel v3.187 Bryony Thompson Changed child panels to: Early-onset Parkinson disease; Ataxia; Brain Channelopathies; Dystonia and Chorea; Paroxysmal Dyskinesia
Infertility and Recurrent Pregnancy Loss v1.132 TEX15 Zornitza Stark Marked gene: TEX15 as ready
Infertility and Recurrent Pregnancy Loss v1.132 TEX15 Zornitza Stark Gene: tex15 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.132 Zornitza Stark Copied gene TEX15 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.132 TEX15 Zornitza Stark gene: TEX15 was added
gene: TEX15 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TEX15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEX15 were set to 26199321; 28355598; 28303806
Phenotypes for gene: TEX15 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4599 RPL10L Lucy Spencer Phenotypes for gene: RPL10L were changed from MONDO_0004983, oligo-/azoospermia to Male infertility MONDO:0005372, RPL10L-related
Mendeliome v1.4598 RPL10L Lucy Spencer Publications for gene: RPL10L were set to PMID:32111475
Mendeliome v1.4597 RPL10L Lucy Spencer reviewed gene: RPL10L: Rating: AMBER; Mode of pathogenicity: None; Publications: 39625557; Phenotypes: Male infertility MONDO:0005372, RPL10L-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.608 Sarah Milton Copied gene TNK2 from panel Mendeliome
Regression v0.608 TNK2 Sarah Milton gene: TNK2 was added
gene: TNK2 was added to Regression. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNK2 were set to 27977884; 23686771; 31517310
Phenotypes for gene: TNK2 were set to late onset infantile epilepsy; Mayer-Rokitansky-Küster-Hauser syndrome
Mendeliome v1.4597 RNF212B Lucy Spencer Phenotypes for gene: RNF212B were changed from Infertility disorder, MONDO:0005047 to Infertility disorder, MONDO:0005047, RNF212B-related
Intellectual disability syndromic and non-syndromic v1.709 Sarah Milton Copied gene TNK2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.709 TNK2 Sarah Milton gene: TNK2 was added
gene: TNK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNK2 were set to 27977884; 23686771; 31517310
Phenotypes for gene: TNK2 were set to late onset infantile epilepsy; Mayer-Rokitansky-Küster-Hauser syndrome
Mendeliome v1.4596 RNF212B Lucy Spencer Publications for gene: RNF212B were set to 37124137
Mendeliome v1.4595 RNF212B Lucy Spencer reviewed gene: RNF212B: Rating: AMBER; Mode of pathogenicity: None; Publications: 37124137, 40259604; Phenotypes: Infertility disorder, MONDO:0005047, RNF212B-related; Mode of inheritance: None
Genetic Epilepsy v1.389 Sarah Milton Added reviews for gene TNK2 from panel Mendeliome
Disorders of immune dysregulation v1.39 Sarah Milton Copied gene TNK2 from panel Mendeliome
Disorders of immune dysregulation v1.39 TNK2 Sarah Milton gene: TNK2 was added
gene: TNK2 was added to Disorders of immune dysregulation. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNK2 were set to 27977884; 23686771; 31517310
Phenotypes for gene: TNK2 were set to late onset infantile epilepsy; Mayer-Rokitansky-Küster-Hauser syndrome
Mendeliome v1.4595 TNK2 Sarah Milton changed review comment from: TNK2 encodes a cytosolic, nonreceptor tyrosine kinase that shows high expression in the brain.

Summary of literature on gene disease association thus far:

Mayer-Rokitansky-Kuster-Hauser syndrome
Single patient reported in PMID: 31517310, no functional studies

Neurodevelopmental disorder, MONDO:0700092
PMID: 39493104, 27977884, 23686771 - 4 families and 7 children affected with infantile onset epilepsy/spasms with associated regression. All had biallelic missense variants in TNK2. No functional studies thus far in regards to epilepsy phenotype.

SLE predisposition
1 family with 2 affected individuals with SLE with compound heterozygous variants in TNK2. Supportive functional studies showing missense variants detected resulted in loss of function, somewhat supportive mouse study.; to: TNK2 encodes a cytosolic, nonreceptor tyrosine kinase that shows high expression in the brain.

Summary of literature on gene disease association thus far:

Mayer-Rokitansky-Kuster-Hauser syndrome
Single patient reported in PMID: 31517310 with monoallelic TNK2 variant, no functional studies

Neurodevelopmental disorder, MONDO:0700092
PMID: 39493104, 27977884, 23686771 - 4 families and 7 children affected with infantile onset epilepsy/spasms with associated regression. All had biallelic missense variants in TNK2. No functional studies thus far in regards to epilepsy phenotype.

SLE predisposition
PMID: 38883731 - 1 family with 2 affected individuals with SLE with compound heterozygous missense variants in TNK2. Supportive functional studies showing missense variants detected resulted in loss of function, somewhat supportive mouse study.
Mendeliome v1.4595 TNK2 Sarah Milton reviewed gene: TNK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 39570652, 39493104, 31517310, 27977884, 23686771; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, Mayer-Rokitansky-Kuster-Hauser syndrome MONDO:0017771, Lupus erythematosus MONDO:0004670; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4595 RIPOR2 Lucy Spencer Publications for gene: RIPOR2 were set to 24958875; 32631815
Mendeliome v1.4594 RIPOR2 Lucy Spencer reviewed gene: RIPOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37164627; Phenotypes: Deafness, autosomal dominant 21, MIM#607017; Mode of inheritance: None
Mendeliome v1.4594 RHOB Lucy Spencer Phenotypes for gene: RHOB were changed from Cerebral Palsy to Cerebral palsy MONDO:0006497, RHOB-related
Mendeliome v1.4593 RHOB Lucy Spencer Publications for gene: RHOB were set to 32989326
Mendeliome v1.4592 RHOB Lucy Spencer edited their review of gene: RHOB: Added comment: PMID: 32989326 2 CP patients de novo for the same missense S73F, absent from gnomad

PMID: 39080495 no new patients, created a KI rabbit model of S73F which showed CP symptoms ie periventricular leukomalacia and spastic-dystonic diplegia. Also showed the variant activates ACAT1 altering lipid levels which may lead to neuronal and white matter damage resulting in CP.

Still only 2 patients with the same variant reported - amber; Changed rating: AMBER; Changed publications: 32989326, 39080495; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v1.48 EPAS1 Zornitza Stark Phenotypes for gene: EPAS1 were changed from Erythrocytosis, familial, 4, MIM# 611783 to Erythrocytosis, familial, 4, MIM# 611783; Hereditary anaemia, MONDO:0016624, EPAS1-related
Red cell disorders v1.47 EPAS1 Zornitza Stark Publications for gene: EPAS1 were set to 18184961; 18378852; 22367913; 18650473
Red cell disorders v1.46 EPAS1 Zornitza Stark edited their review of gene: EPAS1: Added comment: PMID 39613395: reports 3 individuals from 3 unrelated families with heterozygous EPAS1 loss-of-function variants (two de novo frameshifts, one maternally inherited missense) presenting with childhood-onset congenital hypoplastic anaemia characterized by normocytic normochromic anaemia, reticulocytopenia and relative EPO deficiency; additional cardiac and neurological features in some patients. In‑vitro functional assays (Western blot, immunofluorescence, co‑IP, luciferase reporter, qPCR) demonstrate reduced protein abundance, impaired nuclear localisation, defective CBP binding and decreased EPO transcription, supporting pathogenicity.; Changed publications: 18184961, 18378852, 22367913, 18650473, 39613395; Changed phenotypes: Erythrocytosis, familial, 4, MIM# 611783, Hereditary anaemia, MONDO:0016624, EPAS1-related
Mendeliome v1.4592 EPAS1 Zornitza Stark Phenotypes for gene: EPAS1 were changed from Familial erythrocytosis (MIM#611783), AD to Familial erythrocytosis (MIM#611783); Hereditary anaemia, MONDO:0016624, EPAS1-related
Mendeliome v1.4591 EPAS1 Zornitza Stark Publications for gene: EPAS1 were set to 27292716; 19208626
Mendeliome v1.4590 EPAS1 Zornitza Stark edited their review of gene: EPAS1: Changed phenotypes: Hereditary anaemia, MONDO:0016624, EPAS1-related
Mendeliome v1.4590 EPAS1 Zornitza Stark reviewed gene: EPAS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39613395; Phenotypes: Hereditary anemia, MONDO:0016624, EPAS1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4590 DYNC1H1 Zornitza Stark Publications for gene: DYNC1H1 were set to 25512093; 28196890; 21820100; 32788638; 27549087
Mendeliome v1.4589 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: dyneinopathy MONDO:1040031, Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228, Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563, Spinal muscular atrophy, lower extremity-predominant 1, MIM# 158600
Mendeliome v1.4589 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: dyneinopathy MONDO:1040031, Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228, Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Mendeliome v1.4589 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: dyneinopathy MONDO:1040031, Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228
Mendeliome v1.4589 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Added comment: PMID 38848546 reports 47 individuals from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years). Most individuals presented with divergent neurological and multisystem features such as autonomic features, behavioural disorders, movement disorders, and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies, and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. Age-dependent biphasic disease course observed with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, in several cases neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross-River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of NDD manifestations, indicating a role of dynein in anti-viral immunity and neuronal health.; Changed publications: 21820100, 32788638, 27549087, 38848546
Syndromic Retinopathy v0.251 DDX41 Zornitza Stark Marked gene: DDX41 as ready
Syndromic Retinopathy v0.251 DDX41 Zornitza Stark Gene: ddx41 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.251 DDX41 Zornitza Stark Classified gene: DDX41 as Green List (high evidence)
Syndromic Retinopathy v0.251 DDX41 Zornitza Stark Gene: ddx41 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.250 DDX41 Zornitza Stark gene: DDX41 was added
gene: DDX41 was added to Syndromic Retinopathy. Sources: Literature
preprint tags were added to gene: DDX41.
Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX41 were set to 41646732
Phenotypes for gene: DDX41 were set to Inherited retinal dystrophy, MONDO:0019118, DDX41-related
Review for gene: DDX41 was set to GREEN
Added comment: This study reports 13 individuals from nine unrelated families with biallelic DDX41 variants (missense, frameshift and splice‑affecting) presenting with Leber congenital amaurosis / early‑onset severe retinal dystrophy, often accompanied by neurodevelopmental and skeletal anomalies. The variants are ultra‑rare, segregate in an autosomal recessive pattern, and lead to reduced DDX41 protein levels in patient fibroblasts and in a knock‑in mouse retina, with early ERG deficits and progressive photoreceptor loss. Biochemical assays demonstrate impaired RNA binding and protein instability, supporting loss‑of‑function as the disease mechanism.
Sources: Literature
IBMDx study v0.42 DDX41 Zornitza Stark Marked gene: DDX41 as ready
IBMDx study v0.42 DDX41 Zornitza Stark Gene: ddx41 has been classified as Green List (High Evidence).
IBMDx study v0.42 DDX41 Zornitza Stark Mode of inheritance for gene: DDX41 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.185 Chirag Patel Copied gene NRP1 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.185 NRP1 Chirag Patel gene: NRP1 was added
gene: NRP1 was added to Pituitary hormone deficiency. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NRP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP1 were set to 34636164; 28334861
Phenotypes for gene: NRP1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Mendeliome v1.4589 Chirag Patel Copied gene NRP1 from panel Hypogonadotropic hypogonadism
Mendeliome v1.4589 NRP1 Chirag Patel gene: NRP1 was added
gene: NRP1 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NRP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP1 were set to 34636164; 28334861
Phenotypes for gene: NRP1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Hypogonadotropic hypogonadism v0.87 NRP1 Chirag Patel Marked gene: NRP1 as ready
Hypogonadotropic hypogonadism v0.87 NRP1 Chirag Patel Gene: nrp1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.87 NRP1 Chirag Patel gene: NRP1 was added
gene: NRP1 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: NRP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP1 were set to 34636164; 28334861
Phenotypes for gene: NRP1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Review for gene: NRP1 was set to RED
Added comment: PMID 28334861 and PMID 34636164 report a total of 13 individuals (8 families, 8 unrelated) with heterozygous missense NRP1 variants presenting with isolated hypogonadotropic hypogonadism / Kallmann syndrome (childhood‑adolescent onset, anosmia, low gonadotropins). Several variants inherited from unaffected parents. No functional assays were performed, but the variants are rare and predicted loss‑of‑function. Variants are classified as VUS. Oligogenic inheritance in some probands with additional IHH‑associated gene variants.
Sources: Literature
Pituitary hormone deficiency v0.184 NRP2 Chirag Patel Marked gene: NRP2 as ready
Pituitary hormone deficiency v0.184 NRP2 Chirag Patel Gene: nrp2 has been classified as Red List (Low Evidence).
Mendeliome v1.4588 NRP2 Chirag Patel Marked gene: NRP2 as ready
Mendeliome v1.4588 NRP2 Chirag Patel Gene: nrp2 has been classified as Red List (Low Evidence).
Mendeliome v1.4588 Chirag Patel Copied gene NRP2 from panel Hypogonadotropic hypogonadism
Mendeliome v1.4588 NRP2 Chirag Patel gene: NRP2 was added
gene: NRP2 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP2 were set to 34636164; 28334861
Phenotypes for gene: NRP2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Pituitary hormone deficiency v0.184 Chirag Patel Copied gene NRP2 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.184 NRP2 Chirag Patel gene: NRP2 was added
gene: NRP2 was added to Pituitary hormone deficiency. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP2 were set to 34636164; 28334861
Phenotypes for gene: NRP2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel Marked gene: NRP2 as ready
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel Gene: nrp2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel reviewed gene: NRP2: Rating: RED; Mode of pathogenicity: None; Publications: 34636164, 28334861; Phenotypes: Hypogonadotropic hypogonadism MONDO:0018555; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel Deleted their review
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel gene: NRP2 was added
gene: NRP2 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: NRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP2 were set to 34636164; 28334861
Phenotypes for gene: NRP2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: NRP2 was set to GREEN
Added comment: PMID 28334861 reports four individuals with heterozygous NRP2 missense variants presenting with Kallmann syndrome (congenital hypogonadotropic hypogonadism with anosmia). PMID 34636164 reports two unrelated families with heterozygous NRP2 missense variants causing isolated normosmic hypogonadotropic hypogonadism. No functional validation or segregation data were provided for any variant. Variants are too common in population and/or classified as VUS/benign.
Sources: Literature
Hypogonadotropic hypogonadism v0.85 PLXNA1 Chirag Patel Marked gene: PLXNA1 as ready
Hypogonadotropic hypogonadism v0.85 PLXNA1 Chirag Patel Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.183 PLXNA1 Chirag Patel Marked gene: PLXNA1 as ready
Pituitary hormone deficiency v0.183 PLXNA1 Chirag Patel Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.183 Chirag Patel Copied gene PLXNA1 from panel Differences of Sex Development
Pituitary hormone deficiency v0.183 PLXNA1 Chirag Patel gene: PLXNA1 was added
gene: PLXNA1 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PLXNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNA1 were set to 28334861; 30467832; 34636164
Phenotypes for gene: PLXNA1 were set to Hypogonadotropic hypogonadism MONDO:0018555, PLXNA1-related
Hypogonadotropic hypogonadism v0.85 Chirag Patel Copied gene PLXNA1 from panel Differences of Sex Development
Hypogonadotropic hypogonadism v0.85 PLXNA1 Chirag Patel gene: PLXNA1 was added
gene: PLXNA1 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PLXNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNA1 were set to 28334861; 30467832; 34636164
Phenotypes for gene: PLXNA1 were set to Hypogonadotropic hypogonadism MONDO:0018555, PLXNA1-related
Renal Ciliopathies and Nephronophthisis v1.53 TTC26 Chirag Patel Marked gene: TTC26 as ready
Renal Ciliopathies and Nephronophthisis v1.53 TTC26 Chirag Patel Gene: ttc26 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.53 Chirag Patel Copied gene TTC26 from panel Ciliopathies
Renal Ciliopathies and Nephronophthisis v1.53 TTC26 Chirag Patel gene: TTC26 was added
gene: TTC26 was added to Renal Ciliopathies and Nephronophthisis. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 34177428; 32617964; 31595528; 24596149; 22718903
Phenotypes for gene: TTC26 were set to Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534; Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Pituitary hormone deficiency v0.182 TTC26 Chirag Patel Marked gene: TTC26 as ready
Pituitary hormone deficiency v0.182 TTC26 Chirag Patel Gene: ttc26 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.182 Chirag Patel Copied gene TTC26 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.182 TTC26 Chirag Patel gene: TTC26 was added
gene: TTC26 was added to Pituitary hormone deficiency. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 32617964
Phenotypes for gene: TTC26 were set to biliary, renal, neurologic, and skeletal syndrome, MONDO:0859191
Hypogonadotropic hypogonadism v0.84 TTC26 Chirag Patel Marked gene: TTC26 as ready
Hypogonadotropic hypogonadism v0.84 TTC26 Chirag Patel Gene: ttc26 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.84 TTC26 Chirag Patel gene: TTC26 was added
gene: TTC26 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 32617964
Phenotypes for gene: TTC26 were set to biliary, renal, neurologic, and skeletal syndrome, MONDO:0859191
Review for gene: TTC26 was set to RED
Added comment: PMID 32617964 reports 4 individuals from 2 unrelated consanguineous families with the same homozygous TTC26 variant (c.695A>G, p.Asn232Ser) presenting with pituitary stalk interruption syndrome (PSIS) and multiple anterior pituitary hormone deficiencies (GH, ACTH, TSH), micropenis, growth failure, and additional hepatic, renal, cardiac and skeletal anomalies. The phenotype also includes features of hypogonadotropic hypogonadism (micropenis). No functional validation of the missense variant is provided.
Sources: Literature
Pituitary hormone deficiency v0.181 AKT3 Chirag Patel Marked gene: AKT3 as ready
Pituitary hormone deficiency v0.181 AKT3 Chirag Patel Gene: akt3 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.181 AKT3 Chirag Patel gene: AKT3 was added
gene: AKT3 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AKT3 were set to 38459620; 28190287
Phenotypes for gene: AKT3 were set to overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Review for gene: AKT3 was set to RED
Added comment: ClinGen DEFINITIVE association (Jul 2021) with GOF mechanism and only missense variants reported.

PMID 35665751 reports 1 individual with a de novo AKT3 p.Gln78Arg gain‑of‑function variant causing congenital hypothyroidism (thyroid hypogenesis), megalencephaly and polymicrogyria. PMID 38459620 reports 1 individual with a AKT3 p.Asp322Tyr gain‑of‑function variant causing megalencephaly, growth hormone deficiency and central hypothyroidism.


PMID 28190287 reports 1 individual with a de novo AKT3 p.Glu40Lys gain‑of‑function variant causing childhood‑onset megalencephaly, hypotonia, connective‑tissue laxity and growth‑hormone deficiency. PMID 38459620 reports 1 individual with a AKT3 p.Asp322Tyr gain‑of‑function variant causing megalencephaly, growth‑hormone deficiency and central hypothyroidism.
Sources: Literature
Congenital hypothyroidism v0.91 AKT3 Chirag Patel Marked gene: AKT3 as ready
Congenital hypothyroidism v0.91 AKT3 Chirag Patel Gene: akt3 has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.91 AKT3 Chirag Patel gene: AKT3 was added
gene: AKT3 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AKT3 were set to 38459620; 35665751
Phenotypes for gene: AKT3 were set to overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Review for gene: AKT3 was set to RED
Added comment: ClinGen DEFINITIVE association (Jul 2021) with GOF mechanism and only missense variants reported.

PMID 35665751 reports 1 individual with a de novo AKT3 p.Gln78Arg gain‑of‑function variant causing congenital hypothyroidism (thyroid hypogenesis), megalencephaly and polymicrogyria. PMID 38459620 reports 1 individual with a AKT3 p.Asp322Tyr gain‑of‑function variant causing megalencephaly, growth hormone deficiency and central hypothyroidism.
Sources: Literature
Congenital hypothyroidism v0.90 HIST1H1E Chirag Patel Marked gene: HIST1H1E as ready
Congenital hypothyroidism v0.90 HIST1H1E Chirag Patel Gene: hist1h1e has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.90 HIST1H1E Chirag Patel gene: HIST1H1E was added
gene: HIST1H1E was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: HIST1H1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H1E were set to 40444808; 34290007
Phenotypes for gene: HIST1H1E were set to Rahman syndrome, MIM# 617537
Review for gene: HIST1H1E was set to RED
Added comment: Rahman syndrome is characterized by mild to severe intellectual disability associated with variable somatic overgrowth. Some individuals may have other minor anomalies, including dysmorphic facial features, strabismus, or camptodactyly. More than 40 unrelated individuals reported. PTVs result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain.

PMID 34290007 and 40444808 report 2 unrelated individuals with Rahman syndrome with central hypothyroidism.
Sources: Literature
Adrenal insufficiency v0.76 KCNQ1 Chirag Patel edited their review of gene: KCNQ1: Added comment: Additional 1 individual with a rare heterozygous missense KCNQ1 variant (p.P369L) presenting with childhood‑onset central hypothyroidism as part of multiple pituitary hormone deficiency (GH, ACTH, TSH, hypogonadotropic hypogonadism), gingival fibromatosis, dysmorphic facial features, and short stature. The variant was inherited from his unaffected mother.; Changed rating: GREEN; Changed publications: 38987191; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adrenal insufficiency v0.76 KCNQ1 Chirag Patel Phenotypes for gene: KCNQ1 were changed from Hypopituitarism, MONDO:0005152; Long QT syndrome 1 (192500) to Hypopituitarism, MONDO:0005152
Adrenal insufficiency v0.75 KCNQ1 Chirag Patel Publications for gene: KCNQ1 were set to 29097701
Pituitary hormone deficiency v0.180 KCNQ1 Chirag Patel Publications for gene: KCNQ1 were set to 29097701
Congenital hypothyroidism v0.89 KCNQ1 Chirag Patel Publications for gene: KCNQ1 were set to 29097701
Adrenal insufficiency v0.74 KCNQ1 Chirag Patel Classified gene: KCNQ1 as Green List (high evidence)
Adrenal insufficiency v0.74 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.73 Chirag Patel Added reviews for gene KCNQ1 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.88 KCNQ1 Chirag Patel Marked gene: KCNQ1 as ready
Congenital hypothyroidism v0.88 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.88 Chirag Patel Copied gene KCNQ1 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.88 KCNQ1 Chirag Patel gene: KCNQ1 was added
gene: KCNQ1 was added to Congenital hypothyroidism. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KCNQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNQ1 were set to 29097701
Phenotypes for gene: KCNQ1 were set to Hypopituitarism, MONDO:0005152
Adrenal insufficiency v0.72 Chirag Patel Added reviews for gene KCNQ1 from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.179 KCNQ1 Chirag Patel Phenotypes for gene: KCNQ1 were changed from Hypopituitarism, MONDO:0005152; Long QT syndrome 1 (192500) to Hypopituitarism, MONDO:0005152
Pituitary hormone deficiency v0.178 KCNQ1 Chirag Patel Classified gene: KCNQ1 as Green List (high evidence)
Pituitary hormone deficiency v0.178 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.177 KCNQ1 Chirag Patel edited their review of gene: KCNQ1: Added comment: Additional 1 individual with a rare heterozygous missense KCNQ1 variant (p.P369L) presenting with childhood‑onset central hypothyroidism as part of multiple pituitary hormone deficiency (GH, ACTH, TSH, hypogonadotropic hypogonadism), gingival fibromatosis, dysmorphic facial features, and short stature. The variant was inherited from his unaffected mother.; Changed rating: GREEN; Changed publications: 38987191
Mendeliome v1.4587 Chirag Patel Added reviews for gene MAMLD1 from panel Congenital hypothyroidism
Congenital hypothyroidism v0.87 MAMLD1 Chirag Patel Marked gene: MAMLD1 as ready
Congenital hypothyroidism v0.87 MAMLD1 Chirag Patel Gene: mamld1 has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.87 MAMLD1 Chirag Patel gene: MAMLD1 was added
gene: MAMLD1 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: MAMLD1 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: MAMLD1 were set to 36898841
Phenotypes for gene: MAMLD1 were set to Congenital hypothyroidism MONDO:0018612
Review for gene: MAMLD1 was set to RED
Added comment: PMID 36898841 reports 2 individuals from 2 unrelated South East Asian families with hemizygous X‑linked MAMLD1 variants presenting with congenital hypothyroidism due to dyshormonogenesis. Both patients have early‑onset hypothyroidism (30 days and 15 years). Functional assays show gain‑of‑function effects on non‑canonical Notch signalling, increasing HES3 expression and suppressing HES1‑dependent thyroid hormone biosynthesis genes.

However, the non‑frameshift duplication p.Q477dup was maternally inherited and has a relatively high allele frequency in East Asian populations (0.54 %), and the in silico predictions for the de novo missense p.C942Y variant are benign.
Sources: Literature
Congenital hypothyroidism v0.86 OTUD6B Chirag Patel Marked gene: OTUD6B as ready
Congenital hypothyroidism v0.86 OTUD6B Chirag Patel Gene: otud6b has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.86 OTUD6B Chirag Patel Classified gene: OTUD6B as Red List (low evidence)
Congenital hypothyroidism v0.86 OTUD6B Chirag Patel Gene: otud6b has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.85 OTUD6B Chirag Patel reviewed gene: OTUD6B: Rating: RED; Mode of pathogenicity: None; Publications: 41188742, 32924626; Phenotypes: Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, OMIM #617452; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v0.85 Chirag Patel Copied gene OTUD6B from panel Mendeliome
Congenital hypothyroidism v0.85 OTUD6B Chirag Patel gene: OTUD6B was added
gene: OTUD6B was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OTUD6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD6B were set to 28343629; 32924626; 31147255
Phenotypes for gene: OTUD6B were set to Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, OMIM #617452
Hypogonadotropic hypogonadism v0.83 SOX11 Chirag Patel Marked gene: SOX11 as ready
Hypogonadotropic hypogonadism v0.83 SOX11 Chirag Patel Gene: sox11 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.83 Chirag Patel Copied gene SOX11 from panel Differences of Sex Development
Hypogonadotropic hypogonadism v0.83 SOX11 Chirag Patel gene: SOX11 was added
gene: SOX11 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29459093; 24886874; 33086258; 33785884; 35642566; 35341651
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Adrenal insufficiency v0.71 TBCE Chirag Patel Marked gene: TBCE as ready
Adrenal insufficiency v0.71 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Adrenal insufficiency v0.71 TBCE Chirag Patel Classified gene: TBCE as Green List (high evidence)
Adrenal insufficiency v0.71 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Adrenal insufficiency v0.70 TBCE Chirag Patel gene: TBCE was added
gene: TBCE was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to 39086450
Phenotypes for gene: TBCE were set to hypoparathyroidism-retardation-dysmorphism syndrome, MONDO:0009426
Review for gene: TBCE was set to GREEN
Added comment: PMID 33150438 describes a cohort of 63 patients with HRD syndrome, 62 of whom harbor the same homozygous c.155_166del12 deletion and one with homozygous c.207_208delTA. Adrenal glucocorticoid insufficiency was diagnosed in 22% of patients.
Sources: Literature
Congenital hypothyroidism v0.84 TBCE Chirag Patel Marked gene: TBCE as ready
Congenital hypothyroidism v0.84 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.84 TBCE Chirag Patel Classified gene: TBCE as Green List (high evidence)
Congenital hypothyroidism v0.84 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.83 TBCE Chirag Patel gene: TBCE was added
gene: TBCE was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to 39086450; 33150438; 26336027
Phenotypes for gene: TBCE were set to hypoparathyroidism-retardation-dysmorphism syndrome, MONDO:0009426
Review for gene: TBCE was set to GREEN
Added comment: PMID 33150438 describes a cohort of 63 patients with HRD syndrome, 62 of whom harbor the same homozygous c.155_166del12 deletion and one with homozygous c.207_208delTA. Hypothyroidism was found in 36% of patients.

PMID 26336027 reports a Moroccan child with HRD syndrome and congenital hypothyroidism with the homozygous c.155_166del12 deletion.

PMID 39086450 reports a Libyan child with HRD syndrome and congenital hypothyroidism with the homozygous c.155_166del12 deletion.
Sources: Literature
Adrenal insufficiency v0.69 C14orf80 Chirag Patel Marked gene: C14orf80 as ready
Adrenal insufficiency v0.69 C14orf80 Chirag Patel Gene: c14orf80 has been classified as Red List (Low Evidence).
Adrenal insufficiency v0.69 C14orf80 Chirag Patel Classified gene: C14orf80 as Red List (low evidence)
Adrenal insufficiency v0.69 C14orf80 Chirag Patel Gene: c14orf80 has been classified as Red List (Low Evidence).
Adrenal insufficiency v0.68 C14orf80 Chirag Patel gene: C14orf80 was added
gene: C14orf80 was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: C14orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C14orf80 were set to 39979680; 38252227; 30842647
Phenotypes for gene: C14orf80 were set to Syndromic disease, MONDO:0002254
Review for gene: C14orf80 was set to RED
Added comment: Adrenal insufficiency only reported in 2 male siblings from 1 non-consanguineous family with biallelic loss‑of‑function TEDC1 variants (c.104-5C>G and p.Ala263LeufsTer29). They also had prenatal‑onset severe growth impairment, primary microcephaly, primary hypogonadism, congenital glaucoma, craniosynostosis, tracheal stenosis and developmental delay. Functional studies demonstrate loss of TEDC1 protein, disrupted TEDC2 binding, cell‑cycle defects in patient lymphoblastoid cells, and recapitulation of growth and cranial phenotypes in a tedc1‑/‑ zebrafish model.

Total of 5 individuals from 3 families reported with biallelic loss‑of‑function TEDC1 variants, presenting with developmental delay and microcephaly.
Sources: Literature
Adrenal insufficiency v0.67 CPOX Chirag Patel Marked gene: CPOX as ready
Adrenal insufficiency v0.67 CPOX Chirag Patel Gene: cpox has been classified as Green List (High Evidence).
Adrenal insufficiency v0.67 CPOX Chirag Patel Classified gene: CPOX as Green List (high evidence)
Adrenal insufficiency v0.67 CPOX Chirag Patel Gene: cpox has been classified as Green List (High Evidence).
Adrenal insufficiency v0.66 CPOX Chirag Patel gene: CPOX was added
gene: CPOX was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: CPOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPOX were set to 40857591; 40481674; 40296768
Phenotypes for gene: CPOX were set to harderoporphyria, MONDO:0030048
Review for gene: CPOX was set to GREEN
Added comment: ClinGen DEFINITIVE association (Jan 2023).

Childhood‑onset primary adrenal insufficiency reported in 5 individuals from 4 unrelated families with biallelic loss‑of‑function CPOX variants, with 3 individuals also having 46,XY DSD (PMID 40296768 and 40481674).
Sources: Literature
Syndromic Retinopathy v0.249 Sarah Milton Copied gene TOMM7 from panel Mendeliome
Syndromic Retinopathy v0.249 TOMM7 Sarah Milton gene: TOMM7 was added
gene: TOMM7 was added to Syndromic Retinopathy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to 36299998; 36282599
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, MIM# 620601
Microcephaly v1.421 Sarah Milton Copied gene TOMM7 from panel Mendeliome
Microcephaly v1.421 TOMM7 Sarah Milton gene: TOMM7 was added
gene: TOMM7 was added to Microcephaly. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to 36299998; 36282599
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, MIM# 620601
Fetal anomalies v1.544 Sarah Milton Copied gene TOMM7 from panel Mendeliome
Fetal anomalies v1.544 TOMM7 Sarah Milton gene: TOMM7 was added
gene: TOMM7 was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to 36299998; 36282599
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, MIM# 620601
Mendeliome v1.4586 TOMM7 Sarah Milton reviewed gene: TOMM7: Rating: GREEN; Mode of pathogenicity: None; Publications: 39615461, 36299998, 36282599; Phenotypes: Garg-Mishra progeroid syndrome, MIM#620601; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adrenal insufficiency v0.65 GFER Chirag Patel Marked gene: GFER as ready
Adrenal insufficiency v0.65 GFER Chirag Patel Gene: gfer has been classified as Red List (Low Evidence).
Adrenal insufficiency v0.65 GFER Chirag Patel gene: GFER was added
gene: GFER was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: GFER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFER were set to 26018198
Phenotypes for gene: GFER were set to Mitochondrial disease, MONDO:0044970
Review for gene: GFER was set to RED
Added comment: ClinGen DEFINITIVE association with disease (Sep'23).
Only 1 patient aged 19 years reported with infancy onset adrenal insufficiency.
Sources: Literature
Adrenal insufficiency v0.64 HSD17B4 Chirag Patel Marked gene: HSD17B4 as ready
Adrenal insufficiency v0.64 HSD17B4 Chirag Patel Gene: hsd17b4 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.64 HSD17B4 Chirag Patel Classified gene: HSD17B4 as Green List (high evidence)
Adrenal insufficiency v0.64 HSD17B4 Chirag Patel Gene: hsd17b4 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.63 HSD17B4 Chirag Patel gene: HSD17B4 was added
gene: HSD17B4 was added to Adrenal insufficiency. Sources: Literature,ClinGen
Mode of inheritance for gene: HSD17B4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSD17B4 were set to 40416444; 32904102; 32528852
Phenotypes for gene: HSD17B4 were set to d-bifunctional protein deficiency, MONDO:0009855
Review for gene: HSD17B4 was set to GREEN
Added comment: ClinGen DEFINITIVE association with disease (Apr 2020).

Adrenal insufficiency reported in 5 individuals from 3 unrelated families with D‑bifunctional protein deficiency due to biallelic loss‑of‑function HSD17B4 variants.
Sources: Literature, ClinGen
Pituitary hormone deficiency v0.177 MAGEL2 Chirag Patel Marked gene: MAGEL2 as ready
Pituitary hormone deficiency v0.177 MAGEL2 Chirag Patel Gene: magel2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.177 Chirag Patel Copied gene MAGEL2 from panel Mendeliome
Pituitary hormone deficiency v0.177 MAGEL2 Chirag Patel gene: MAGEL2 was added
gene: MAGEL2 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: MAGEL2 were set to 33820833; 24076603; 31397880; 29599419; 30302899
Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome, MIM# 615547
Mendeliome v1.4586 KLHL15 Sangavi Sivagnanasundram changed review comment from: A male individual presenting with impaired intelligence, short stature, frequent hypoglycaemia and periodic fever.
Hemizygous variant was identified in the proband c.736 C>T p.(Arg246*) - absent from gnomAD v4.1; to: Additional male individual presenting with impaired intelligence, short stature, frequent hypoglycaemia and periodic fever.
Hemizygous variant was identified in the proband c.736 C>T p.(Arg246*) - absent from gnomAD v4.1
Mendeliome v1.4586 KLHL15 Sangavi Sivagnanasundram reviewed gene: KLHL15: Rating: GREEN; Mode of pathogenicity: None; Publications: 37452054; Phenotypes: intellectual disability, X-linked 103 MONDO:0010508; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Adrenal insufficiency v0.62 FOXA2 Chirag Patel Marked gene: FOXA2 as ready
Adrenal insufficiency v0.62 FOXA2 Chirag Patel Gene: foxa2 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.62 PROP1 Chirag Patel Marked gene: PROP1 as ready
Adrenal insufficiency v0.62 PROP1 Chirag Patel Gene: prop1 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.62 PROP1 Chirag Patel changed review comment from: Well-established gene-disease association; Over 30 unrelated families with homozygous/ compound heterozygous (small deletions, frameshift, insertions, missense, nonsense and splice) PROP1 variants. The majority of patients present with complete absence of puberty, dwarfism and low GH, PRL, TSH, LH, and FSH associated with severe hypoplasia of the pituitary gland. Most affected individuals are ascertained due to growth failure (early childhood) and failure to thrive starting in infancy.; to: Well-established gene-disease association; Over 30 unrelated families with homozygous/ compound heterozygous (small deletions, frameshift, insertions, missense, nonsense and splice) PROP1 variants. The majority of patients present with complete absence of puberty, dwarfism and low GH, PRL, TSH, LH, and FSH associated with severe hypoplasia of the pituitary gland. Most affected individuals are ascertained due to growth failure (early childhood) and failure to thrive starting in infancy.

10 individuals developed progressive ACTH deficiency around mid 20s.
Adrenal insufficiency v0.62 Chirag Patel Copied gene PROP1 from panel Pituitary hormone deficiency
Adrenal insufficiency v0.62 PROP1 Chirag Patel gene: PROP1 was added
gene: PROP1 was added to Adrenal insufficiency. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PROP1 were set to 20301521, 31090814
Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined, 2 MIM# 262600
Adrenal insufficiency v0.61 Chirag Patel Copied gene FOXA2 from panel Pituitary hormone deficiency
Adrenal insufficiency v0.61 FOXA2 Chirag Patel gene: FOXA2 was added
gene: FOXA2 was added to Adrenal insufficiency. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: FOXA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXA2 were set to 28973288, 29329447, 30414530, 33729509, 31294511, 33999151
Phenotypes for gene: FOXA2 were set to Hypopituitarism, MONDO:0005152; Hyperinsulinism, MONDO:0002177
Adrenal insufficiency v0.60 IARS2 Chirag Patel Marked gene: IARS2 as ready
Adrenal insufficiency v0.60 IARS2 Chirag Patel Gene: iars2 has been classified as Amber List (Moderate Evidence).
Adrenal insufficiency v0.60 IARS2 Chirag Patel Classified gene: IARS2 as Amber List (moderate evidence)
Adrenal insufficiency v0.60 IARS2 Chirag Patel Gene: iars2 has been classified as Amber List (Moderate Evidence).
Adrenal insufficiency v0.59 IARS2 Chirag Patel gene: IARS2 was added
gene: IARS2 was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: IARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS2 were set to 30419932
Phenotypes for gene: IARS2 were set to cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome, MONDO:0014455
Review for gene: IARS2 was set to AMBER
Added comment: Established gene-disease association with cataract‑growth hormone deficiency‑sensory neuropathy‑sensorineural hearing loss‑skeletal dysplasia (CAGSSS) syndrome.

PMID 30419932 reports 2 unrelated individuals with the same homozygous missense variant in IARS2 gene (p.Pro909Ser) presenting with CAGSSS syndrome and central adrenal insufficiency.
Sources: Literature
Mendeliome v1.4586 POU3F4 upstream regulatory region Sarah Milton Region: POU3F4 upstream regulatory region was added
Region: POU3F4 upstream regulatory region was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: POU3F4 upstream regulatory region was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for Region: POU3F4 upstream regulatory region were set to PMID: 41170199, 35189936, 33860785
Phenotypes for Region: POU3F4 upstream regulatory region were set to Deafness, X-linked 2 MIM#304400
Review for Region: POU3F4 upstream regulatory region was set to AMBER
Added comment: POU3F4 encodes POU domain, class III, transcriptional factor 4, a transcription factor with functional targets not fully elucidated but known to affect expression of GJB6, EPHA4 and EFNB2 in development.

17 patients reported across a number of publications with deletions sized between 8kb to 1.74mb upstream of POU3F4 presented with X linked deafness.

Yang et al PMID: 41170199 reported 4 male individuals from one pedigree with deafness segregating with the upstream deletion.
qPCR demonstrated reduced mRNA expression of POU3F4 in two affected males with the deletion with normal levels in their unaffected father.

It is proposed this deletion is removing an upstream enhancer element however functional studies have not been performed to demonstrate this as of yet.

The coordinates used in this entry are the largest reported to cause the phenotype most deletions reported in affected individuals were smaller.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.204 Chirag Patel Added reviews for gene WNT4 from panel Adrenal insufficiency
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.203 WNT4 Chirag Patel Marked gene: WNT4 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.203 WNT4 Chirag Patel Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.203 WNT4 Chirag Patel Classified gene: WNT4 as Amber List (moderate evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.203 WNT4 Chirag Patel Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4585 Chirag Patel Added reviews for gene WNT4 from panel Adrenal insufficiency
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.202 Chirag Patel Added reviews for gene WNT4 from panel Adrenal insufficiency
Adrenal insufficiency v0.58 WNT4 Chirag Patel Classified gene: WNT4 as Amber List (moderate evidence)
Adrenal insufficiency v0.58 WNT4 Chirag Patel Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Adrenal insufficiency v0.57 WNT4 Chirag Patel edited their review of gene: WNT4: Added comment: A male fetus from consanguineous family with features of SERKAL syndrome (bilateral diaphragma genesis, pulmonary hypoplasia, bilateral renal hypoplasia with cystic dysplasia, RT adrenal agenesis, LT adrenal hypoplasia), and a homozygous missense variant in WNT4 gene (T291R) with parents as heterozygous carriers. Wnt4 -/- mice had ventricular septal defects, small/absent kidneys, sac hernias of diaphragm, and cleft soft palate.; Changed rating: AMBER; Changed publications: 40992710
Mendeliome v1.4584 KIF3B Sangavi Sivagnanasundram changed review comment from: Addtional publication to support review from 2020
"2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking."

GDA to remain as AMBER; to: Addition of publication to support review from 2020
"2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking."

GDA to remain as AMBER
Mendeliome v1.4584 KIF3B Sangavi Sivagnanasundram reviewed gene: KIF3B: Rating: AMBER; Mode of pathogenicity: None; Publications: 34455394; Phenotypes: ciliopathy MONDO:0005308; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.248 TRANK1 Chirag Patel Marked gene: TRANK1 as ready
Autism v0.248 TRANK1 Chirag Patel Gene: trank1 has been classified as Red List (Low Evidence).
Autism v0.248 Chirag Patel Copied gene TRANK1 from panel Mendeliome
Autism v0.248 TRANK1 Chirag Patel gene: TRANK1 was added
gene: TRANK1 was added to Autism. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TRANK1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRANK1 were set to 38649688; 30504930
Phenotypes for gene: TRANK1 were set to Autism, MONDO:0005260
Mendeliome v1.4584 TRANK1 Chirag Patel Marked gene: TRANK1 as ready
Mendeliome v1.4584 TRANK1 Chirag Patel Gene: trank1 has been classified as Red List (Low Evidence).
Mendeliome v1.4584 TRANK1 Chirag Patel gene: TRANK1 was added
gene: TRANK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRANK1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRANK1 were set to 38649688; 30504930
Phenotypes for gene: TRANK1 were set to Autism, MONDO:0005260
Review for gene: TRANK1 was set to RED
Added comment: PMID 30504930 describes 2 unrelated individuals with de novo TRANK1 missense variants (p.Val901Ile and p.Thr2109Lys) and autism spectrum disorder (ASD). No functional studies.

PMID 38649688 identifies 2 brothers from a consanguineous family with a homozygous TRANK1 missense variant (p.Glu273Gly) presenting with ASD, non‑verbal status and associated behavioural traits. Parents heterozygous carriers with no phenotype. No functional studies.
Sources: Literature
Ichthyosis and Porokeratosis v1.25 GLTP Chirag Patel Marked gene: GLTP as ready
Ichthyosis and Porokeratosis v1.25 GLTP Chirag Patel Gene: gltp has been classified as Green List (High Evidence).
Ichthyosis and Porokeratosis v1.25 Chirag Patel Copied gene GLTP from panel Mendeliome
Ichthyosis and Porokeratosis v1.25 GLTP Chirag Patel gene: GLTP was added
gene: GLTP was added to Ichthyosis and Porokeratosis. Sources: Expert Review Green,Literature
Mode of inheritance for gene: GLTP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLTP were set to 41642656
Phenotypes for gene: GLTP were set to Ichthyosis, MONDO:0019269; Epidermal differentiation disorder
Mendeliome v1.4583 GLTP Chirag Patel Marked gene: GLTP as ready
Mendeliome v1.4583 GLTP Chirag Patel Gene: gltp has been classified as Green List (High Evidence).
Mendeliome v1.4583 GLTP Chirag Patel Classified gene: GLTP as Green List (high evidence)
Mendeliome v1.4583 GLTP Chirag Patel Gene: gltp has been classified as Green List (High Evidence).
Mendeliome v1.4582 GLTP Chirag Patel gene: GLTP was added
gene: GLTP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GLTP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLTP were set to 41642656
Phenotypes for gene: GLTP were set to Ichthyosis, MONDO:0019269; Epidermal differentiation disorder
Review for gene: GLTP was set to GREEN
Added comment: PMID 41642656 reports 6 individuals from 5 unrelated families with rare biallelic loss‑of‑function GLTP variants (c.58_62del, c.98delT, c.162+2T>C). Individuals presented with non-syndromic epidermal differentiation disorder (generalized scaling, hyperkeratosis, and pruritus from birth, without extra‑dermal anomalies). GLTP encodes a glycolipid transfer protein that mediates inter‑membrane transport of glucosylceramide. The variants segregated with disease. Functional studies (CRISPR mouse knockout, keratinocyte knockdown, and rescue by eliglustat) demonstrate loss of GLTP expression and disrupted GlcCer trafficking, supporting a loss‑of‑function disease mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.708 Sarah Milton Added reviews for gene KDM5B from panel Mendeliome
Autism v0.247 Sarah Milton Added reviews for gene KDM5B from panel Mendeliome
Mendeliome v1.4581 KDM5B Sarah Milton reviewed gene: KDM5B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37231097; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KDM5B-related, Intellectual developmental disorder, autosomal recessive 65 (MIM#618109); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.149 CD99L2 Chirag Patel Marked gene: CD99L2 as ready
Hereditary Spastic Paraplegia v1.149 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Ataxia v1.195 CD99L2 Chirag Patel Marked gene: CD99L2 as ready
Ataxia v1.195 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.149 Chirag Patel Copied gene CD99L2 from panel Mendeliome
Hereditary Spastic Paraplegia v1.149 CD99L2 Chirag Patel gene: CD99L2 was added
gene: CD99L2 was added to Hereditary Spastic Paraplegia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CD99L2 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: CD99L2 were set to 41690933
Phenotypes for gene: CD99L2 were set to Neurodevelopmental disorder, MONDO:0700092; CD99L2-related
Ataxia v1.195 Chirag Patel Copied gene CD99L2 from panel Mendeliome
Ataxia v1.195 CD99L2 Chirag Patel gene: CD99L2 was added
gene: CD99L2 was added to Ataxia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CD99L2 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: CD99L2 were set to 41690933
Phenotypes for gene: CD99L2 were set to Neurodevelopmental disorder, MONDO:0700092; CD99L2-related
Mendeliome v1.4581 CD99L2 Chirag Patel Phenotypes for gene: CD99L2 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder, MONDO:0700092; CD99L2-related
Mendeliome v1.4580 CD99L2 Chirag Patel Marked gene: CD99L2 as ready
Mendeliome v1.4580 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Marked gene: PDS5A as ready
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Tag preprint tag was added to gene: PDS5A.
Mendeliome v1.4580 CD99L2 Chirag Patel Classified gene: CD99L2 as Green List (high evidence)
Mendeliome v1.4580 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4579 CD99L2 Chirag Patel Classified gene: CD99L2 as Green List (high evidence)
Mendeliome v1.4579 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Mendeliome v1.4578 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Mendeliome v1.4578 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.706 PDS5B Chirag Patel Classified gene: PDS5B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.706 PDS5B Chirag Patel Gene: pds5b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4577 PDS5A Chirag Patel Tag preprint tag was added to gene: PDS5A.
Intellectual disability syndromic and non-syndromic v1.705 PDS5B Chirag Patel Tag preprint tag was added to gene: PDS5B.
Mendeliome v1.4577 PDS5B Chirag Patel Tag preprint tag was added to gene: PDS5B.
Mendeliome v1.4577 PDS5B Chirag Patel Classified gene: PDS5B as Amber List (moderate evidence)
Mendeliome v1.4577 PDS5B Chirag Patel Gene: pds5b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4576 CD99L2 Chirag Patel gene: CD99L2 was added
gene: CD99L2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CD99L2 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: CD99L2 were set to 41690933
Phenotypes for gene: CD99L2 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: CD99L2 was set to GREEN
Added comment: PMID 41690933 identified loss‑of‑function variants in CD99L2 gene in 25 males from 20 unrelated families with X-linked spastic ataxia. The age of onset ranged from 10-68yrs, and the main presenting features were gait disturbances and spasticity (mostly lower limbs), ataxia, dysarthria, oculomotor abnormalities, sensory deficits, and dysphagia. Only 2/19 individuals had cerebellar atrophy on MRI brain. Only 1/4 female carriers had any clinical features.

RNA‑seq showed reduced CD99L2 transcripts and western blot demonstrated loss of full‑length protein. Loss of CD99L2 in patients’ fibroblasts triggered transcriptional dysregulation of genes linked to neuronal and synaptic function. Ablation of cytoplasmic or extracellular domains of CD99L2 lead to its intracellular mislocalisation and abrogation of its interplay with CAPN1 (a calcium-dependent cysteine protease involved in neuronal plasticity).
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.705 Chirag Patel Copied gene PDS5B from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.705 PDS5B Chirag Patel gene: PDS5B was added
gene: PDS5B was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PDS5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDS5B were set to 10.64898/2026.02.23.26346364
Phenotypes for gene: PDS5B were set to Neurodevelopmental disorder, MONDO:0700092
Intellectual disability syndromic and non-syndromic v1.705 Chirag Patel Copied gene PDS5A from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.705 PDS5A Chirag Patel gene: PDS5A was added
gene: PDS5A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PDS5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDS5A were set to 10.64898/2026.02.23.26346364; 30158690
Phenotypes for gene: PDS5A were set to Complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.4575 PDS5A Chirag Patel changed review comment from: Boone 2026 reports 8 individuals from 8 unrelated families with heterozygous predicted damaging PDS5A variants (5 missense and 3 frameshift) and variable neurodevelopmental features without a unified syndrome. Inheritance of variants was 4 de novo, 2 unknown, and 2 inherited from unaffected parent.

PMID 30158690 reports 2 individuals from 2 unrelated families with heterozygous loss‑of‑function PDS5A variants and a CdLS‑like cohesinopathy. One individual had a paternally inherited PDS5A variant (p.E759*) and de novo ASXL3 variant (which explained most of phenotype). The other individual had a de novo PDS5A variant (c.654+5G>C).

No functional studies were presented.
Sources: Literature; to: Boone 2026 reports 8 individuals from 8 unrelated families with rare heterozygous predicted damaging PDS5A variants (5 missense and 3 frameshift) and variable neurodevelopmental features without a unified syndrome. Inheritance of variants was 4 de novo, 2 unknown, and 2 inherited from unaffected parent.

PMID 30158690 reports 2 individuals from 2 unrelated families with heterozygous loss‑of‑function PDS5A variants and a CdLS‑like cohesinopathy. One individual had a paternally inherited PDS5A variant (p.E759*) and de novo ASXL3 variant (which explained most of phenotype). The other individual had a de novo PDS5A variant (c.654+5G>C).

No functional studies were presented.
Sources: Literature
Mendeliome v1.4575 PDS5B Chirag Patel changed review comment from: Boone 2026 reports 8 individuals from 8 unrelated families with rare heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature; to: Boone 2026 reports 8 individuals from 8 unrelated families with rare heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature
Mendeliome v1.4575 PDS5B Chirag Patel changed review comment from: Boone 2026 reports 8 individuals from 8 unrelated families with heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature; to: Boone 2026 reports 8 individuals from 8 unrelated families with rare heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature
Mendeliome v1.4575 PDS5B Chirag Patel Classified gene: PDS5B as Green List (high evidence)
Mendeliome v1.4575 PDS5B Chirag Patel Gene: pds5b has been classified as Green List (High Evidence).
Mendeliome v1.4574 PDS5B Chirag Patel Marked gene: PDS5B as ready
Mendeliome v1.4574 PDS5B Chirag Patel Gene: pds5b has been classified as Red List (Low Evidence).
Mendeliome v1.4574 PDS5B Chirag Patel gene: PDS5B was added
gene: PDS5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDS5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDS5B were set to 10.64898/2026.02.23.26346364
Phenotypes for gene: PDS5B were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: PDS5B was set to GREEN
Added comment: Boone 2026 reports 8 individuals from 8 unrelated families with heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.704 FMO4 Chirag Patel Marked gene: FMO4 as ready
Intellectual disability syndromic and non-syndromic v1.704 FMO4 Chirag Patel Gene: fmo4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.704 Chirag Patel Copied gene FMO4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.704 FMO4 Chirag Patel gene: FMO4 was added
gene: FMO4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: FMO4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FMO4 were set to 41714691, 28940097
Phenotypes for gene: FMO4 were set to Neurodevelopmental disorder, MONDO:0700092; FMO4 related
Mendeliome v1.4573 Chirag Patel Added reviews for gene PDS5A from panel Mendeliome
Mendeliome v1.4572 PDS5A Chirag Patel Marked gene: PDS5A as ready
Mendeliome v1.4572 PDS5A Chirag Patel Gene: pds5a has been classified as Green List (High Evidence).
Mendeliome v1.4572 PDS5A Chirag Patel Classified gene: PDS5A as Green List (high evidence)
Mendeliome v1.4572 PDS5A Chirag Patel Gene: pds5a has been classified as Green List (High Evidence).
Mendeliome v1.4571 PDS5A Chirag Patel gene: PDS5A was added
gene: PDS5A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDS5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDS5A were set to 10.64898/2026.02.23.26346364; 30158690
Phenotypes for gene: PDS5A were set to Complex neurodevelopmental disorder, MONDO:0100038
Review for gene: PDS5A was set to GREEN
Added comment: Boone 2026 reports 8 individuals from 8 unrelated families with heterozygous predicted damaging PDS5A variants (5 missense and 3 frameshift) and variable neurodevelopmental features without a unified syndrome. Inheritance of variants was 4 de novo, 2 unknown, and 2 inherited from unaffected parent.

PMID 30158690 reports 2 individuals from 2 unrelated families with heterozygous loss‑of‑function PDS5A variants and a CdLS‑like cohesinopathy. One individual had a paternally inherited PDS5A variant (p.E759*) and de novo ASXL3 variant (which explained most of phenotype). The other individual had a de novo PDS5A variant (c.654+5G>C).

No functional studies were presented.
Sources: Literature
Mendeliome v1.4570 Chirag Patel Added reviews for gene FMO4 from panel Mendeliome
Mendeliome v1.4569 FMO4 Chirag Patel Marked gene: FMO4 as ready
Mendeliome v1.4569 FMO4 Chirag Patel Gene: fmo4 has been classified as Red List (Low Evidence).
Mendeliome v1.4569 FMO4 Chirag Patel gene: FMO4 was added
gene: FMO4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FMO4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FMO4 were set to 41714691, 28940097
Phenotypes for gene: FMO4 were set to Neurodevelopmental disorder, MONDO:0700092; FMO4 related
Review for gene: FMO4 was set to RED
Added comment: 3 individuals from 2 unrelated families with mild‑moderate intellectual disability without additional systemic features. One family had a homozygous loss-of-function frameshift (p.(Ala520GlyfsTer13)) and the other had a homozygous missense variant (p.(Pro28His)) in FMO4 gene. Parents were heterozygous carriers. No functional validation was performed, but the gene is expressed in the brain and the variants are ultra‑rare in population databases.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.131 SPIDR Chirag Patel Classified gene: SPIDR as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.131 SPIDR Chirag Patel Gene: spidr has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.406 SPIDR Chirag Patel Classified gene: SPIDR as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.406 SPIDR Chirag Patel Gene: spidr has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.405 Chirag Patel Added reviews for gene SPIDR from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.130 Chirag Patel Added reviews for gene SPIDR from panel Mendeliome
Mendeliome v1.4568 SPIDR Chirag Patel Classified gene: SPIDR as Green List (high evidence)
Mendeliome v1.4568 SPIDR Chirag Patel Gene: spidr has been classified as Green List (High Evidence).
Mendeliome v1.4567 SPIDR Chirag Patel reviewed gene: SPIDR: Rating: GREEN; Mode of pathogenicity: None; Publications: 41644825; Phenotypes: Primary ovarian failure, MONDO:0005387; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.106 BICC1 Chirag Patel edited their review of gene: BICC1: Added comment: PMID 41677782 provides 4 individuals from 3 families with very early‑onset polycystic kidney disease (VEO-PKD).
-2 siblings from consanguineous family with homozygous missense BICC1 variant (p.Ser240Pro)(absent gnomAD). One of the siblings also had a PKD2 variant (c.1445T>G, p.Phe482Cys).
-1 individual with BICC1 missense variant (c.2462G>A, p.Gly821Glu)(3025 HTZ gnomAD) inherited from his father (2 small renal cysts in 1 kidney), and a de novo PKD2 variant (c.1894T>C, p.Cys632Arg).
-1 individual with BICC1 splice variant (c.1179+1G>T)(absent gnomAD) inherited from his father, and a de novo PKD1 variant (c.11942C>T, p.Ala3981Val).

Functional assays of the p.Ser240Pro and p.Gly821Glu variants demonstrated hypomorphic loss‑of‑function (CRISPR knock‑in HEK293T, Xenopus rescue, protein stability). Hypothesis that BICC1 cooperates functionally with PKD1 and PKD2, and that BICC1 variants may aggravate PKD severity.; Changed publications: 41677782; Changed phenotypes: Polycystic kidney disease, MONDO:0020642; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.106 Chirag Patel Added reviews for gene BICC1 from panel Mendeliome
Mendeliome v1.4567 Chirag Patel Added reviews for gene BICC1 from panel Mendeliome
Mendeliome v1.4566 BICC1 Chirag Patel edited their review of gene: BICC1: Added comment: PMID 41677782 provides 4 individuals from 3 families with very early‑onset polycystic kidney disease (VEO-PKD).
-2 siblings from consanguineous family with homozygous missense BICC1 variant (p.Ser240Pro)(absent gnomAD). One of the siblings also had a PKD2 variant (c.1445T>G, p.Phe482Cys).
-1 individual with BICC1 missense variant (c.2462G>A, p.Gly821Glu)(3025 HTZ gnomAD) inherited from his father (2 small renal cysts in 1 kidney), and a de novo PKD2 variant (c.1894T>C, p.Cys632Arg).
-1 individual with BICC1 splice variant (c.1179+1G>T)(absent gnomAD) inherited from his father, and a de novo PKD1 variant (c.11942C>T, p.Ala3981Val).
Functional assays of the p.Ser240Pro and p.Gly821Glu variants demonstrated hypomorphic loss‑of‑function (CRISPR knock‑in HEK293T, Xenopus rescue, protein stability). Hypothesis that BICC1 cooperates functionally with PKD1 and PKD2, and that BICC1 variants may aggravate PKD severity.; Changed publications: 41677782; Changed phenotypes: Polycystic kidney disease, MONDO:0020642; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe early-onset obesity v1.30 AGRP Zornitza Stark Marked gene: AGRP as ready
Severe early-onset obesity v1.30 AGRP Zornitza Stark Gene: agrp has been classified as Red List (Low Evidence).
Severe early-onset obesity v1.30 Zornitza Stark Copied gene AGRP from panel Mendeliome
Severe early-onset obesity v1.30 AGRP Zornitza Stark gene: AGRP was added
gene: AGRP was added to Severe early-onset obesity. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: AGRP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGRP were set to 41680086
Phenotypes for gene: AGRP were set to {Leanness, inherited} 601665; {Obesity, late-onset} 601665; Obesity disorder, MONDO:0011122, AGRP-related
Mendeliome v1.4566 AGRP Zornitza Stark Phenotypes for gene: AGRP were changed from {Leanness, inherited} 601665; {Obesity, late-onset} 601665 to {Leanness, inherited} 601665; {Obesity, late-onset} 601665; Obesity disorder, MONDO:0011122, AGRP-related
Mendeliome v1.4565 AGRP Zornitza Stark Publications for gene: AGRP were set to
Mendeliome v1.4564 AGRP Zornitza Stark Mode of inheritance for gene: AGRP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4563 AGRP Zornitza Stark edited their review of gene: AGRP: Added comment: PMID 41680086 reports a single individual carrying a heterozygous missense AGRP variant p.Arg79Cys associated with severe early‑onset childhood obesity; segregation analysis confirms co‑segregation; no functional studies were performed.; Changed publications: 41680086; Changed phenotypes: Obesity disorder, MONDO:0011122, AGRP-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v1.129 C11orf80 Zornitza Stark Phenotypes for gene: C11orf80 were changed from Recurrent hydatidiform mole 4, MIM # 618432 to Infertility disorder, MONDO:0005047, C11orf80-related; hydatidiform mole, recurrent, 4, MONDO:0032747
Infertility and Recurrent Pregnancy Loss v1.128 C11orf80 Zornitza Stark Publications for gene: C11orf80 were set to 30388401; 36732965
Infertility and Recurrent Pregnancy Loss v1.127 C11orf80 Zornitza Stark reviewed gene: C11orf80: Rating: AMBER; Mode of pathogenicity: None; Publications: 41644825, 30388401; Phenotypes: Infertility disorder, MONDO:0005047, C11orf80-related, hydatidiform mole, recurrent, 4, MONDO:0032747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4563 C11orf80 Zornitza Stark Phenotypes for gene: C11orf80 were changed from Recurrent hydatidiform mole 4, MIM # 618432 to Infertility disorder, MONDO:0005047, C11orf80-related; hydatidiform mole, recurrent, 4, MONDO:0032747
Mendeliome v1.4562 C11orf80 Zornitza Stark Publications for gene: C11orf80 were set to 30388401; 36732965
Mendeliome v1.4561 C11orf80 Zornitza Stark edited their review of gene: C11orf80: Added comment: PMID 41644825 reports a Turkish consanguineous family with a homozygous splice‑site TOP6BL variant (c.523+1G>C) causing adult‑onset non‑obstructive azoospermia (NOA) and meiotic arrest; mouse Top6bl knockout recapitulates the male‑infertility phenotype. PMID 30388401 describes two unrelated families with biallelic TOP6BL loss‑of‑function alleles (c.783dup and c.1501T>C) presenting with recurrent complete hydatidiform mole (CHM) and miscarriage.

Maintain Amber rating as unclear whether these two disease associations are related or distinct.; Changed publications: 41644825, 30388401; Changed phenotypes: Infertility disorder, MONDO:0005047, C11orf80-related, hydatidiform mole, recurrent, 4, MONDO:0032747
Deafness_IsolatedAndComplex v1.335 TNC Zornitza Stark Publications for gene: TNC were set to 23936043
Deafness_IsolatedAndComplex v1.334 TNC Zornitza Stark Classified gene: TNC as Green List (high evidence)
Deafness_IsolatedAndComplex v1.334 TNC Zornitza Stark Gene: tnc has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.333 TNC Zornitza Stark edited their review of gene: TNC: Added comment: Five additional unrelated families (12 patients) with heterozygous loss‑of‑function TNC variants (frameshift c.5738_5745dup, nonsense c.1615C>T, nonsense c.1641C>A, missense c.2852C>T, splice‑site c.5247A>T) reported in association with deafness. Phenotypes range from childhood‑onset fluctuating loss to adult low‑frequency progressive loss. Two of the variants are present at relatively high pop frequencies in gnomAD.; Changed rating: GREEN; Changed publications: 23936043, 40203778, 39720982, 39020321, 38640279, 35062939
Mendeliome v1.4561 TNC Zornitza Stark Publications for gene: TNC were set to 23936043; 34093110; 33763067
Mendeliome v1.4560 TNC Zornitza Stark Classified gene: TNC as Green List (high evidence)
Mendeliome v1.4560 TNC Zornitza Stark Gene: tnc has been classified as Green List (High Evidence).
Mendeliome v1.4559 TNC Zornitza Stark edited their review of gene: TNC: Added comment: Five additional unrelated families (12 patients) with heterozygous loss‑of‑function TNC variants (frameshift c.5738_5745dup, nonsense c.1615C>T, nonsense c.1641C>A, missense c.2852C>T, splice‑site c.5247A>T) reported in association with deafness. Phenotypes range from childhood‑onset fluctuating loss to adult low‑frequency progressive loss.

Two of the variants are present at relatively high pop frequencies in gnomAD.; Changed rating: GREEN; Changed publications: 40203778, 39720982, 39020321, 38640279, 35062939; Changed phenotypes: autosomal dominant nonsyndromic hearing loss 56, MONDO:0014283
Congenital Heart Defect v0.531 MYH6 Sangavi Sivagnanasundram Phenotypes for gene: MYH6 were changed from to MYH-6 related congenital heart defects MONDO:0800442
Congenital Heart Defect v0.530 MYH6 Sangavi Sivagnanasundram Mode of inheritance for gene: MYH6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.529 MYH6 Sangavi Sivagnanasundram reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008375; Phenotypes: MYH-6 related congenital heart defects MONDO:0800442; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v1.18 NRDC Zornitza Stark Marked gene: NRDC as ready
Arthrogryposis v1.18 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Genetic Epilepsy v1.388 NRDC Zornitza Stark Classified gene: NRDC as Green List (high evidence)
Genetic Epilepsy v1.388 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Genetic Epilepsy v1.387 NRDC Zornitza Stark Source Literature was added to NRDC.
Rating Changed from No List (delete) to Red List (low evidence)
Genetic Epilepsy v1.386 NRDC Zornitza Stark All sources for gene: NRDC were removed
Arthrogryposis v1.18 Zornitza Stark Copied gene NRDC from panel Mendeliome
Arthrogryposis v1.18 NRDC Zornitza Stark gene: NRDC was added
gene: NRDC was added to Arthrogryposis. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654
Phenotypes for gene: NRDC were set to Neurodevelopmental disorder, MONDO:0700092, NRDC-related
Genetic Epilepsy v1.385 NRDC Zornitza Stark Marked gene: NRDC as ready
Genetic Epilepsy v1.385 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Genetic Epilepsy v1.385 Zornitza Stark Copied gene NRDC from panel Intellectual disability syndromic and non-syndromic
Genetic Epilepsy v1.385 NRDC Zornitza Stark gene: NRDC was added
gene: NRDC was added to Genetic Epilepsy. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: NRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654; 41734767; 41449824
Phenotypes for gene: NRDC were set to Neurodevelopmental disorder, MONDO:0700092, NRDC-related
Intellectual disability syndromic and non-syndromic v1.703 NRDC Zornitza Stark Marked gene: NRDC as ready
Intellectual disability syndromic and non-syndromic v1.703 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.703 NRDC Zornitza Stark Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654
Intellectual disability syndromic and non-syndromic v1.702 NRDC Zornitza Stark Classified gene: NRDC as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.702 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.701 NRDC Zornitza Stark reviewed gene: NRDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41734767, 41449824, 28017472; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NRDC-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.420 NRDC Zornitza Stark Marked gene: NRDC as ready
Microcephaly v1.420 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Microcephaly v1.420 NRDC Zornitza Stark Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654
Microcephaly v1.419 NRDC Zornitza Stark Classified gene: NRDC as Green List (high evidence)
Microcephaly v1.419 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Microcephaly v1.418 NRDC Zornitza Stark reviewed gene: NRDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41734767, 41449824, 28017472; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NRDC-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4559 NRDC Zornitza Stark Marked gene: NRDC as ready
Mendeliome v1.4559 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Mendeliome v1.4559 NRDC Zornitza Stark Classified gene: NRDC as Green List (high evidence)
Mendeliome v1.4559 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Mendeliome v1.4558 NRDC Zornitza Stark reviewed gene: NRDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41734767, 41449824, 28017472; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NRDC-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4558 Bryony Thompson Copied gene RPS27A from panel Haematological malignancies
Mendeliome v1.4558 RPS27A Bryony Thompson gene: RPS27A was added
gene: RPS27A was added to Mendeliome. Sources: Expert Review Red,Curated sources
Mode of inheritance for gene: RPS27A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPS27A were set to 28297620; 24680683; 26942564
Phenotypes for gene: RPS27A were set to Osteosarcoma, soft tissue sarcomas; Diamond Blackfan Anemia; MDS, AML; Class: BM failure syndrome (typ AR)
Mendeliome v1.4557 Bryony Thompson Copied gene RPL36 from panel Haematological malignancies
Mendeliome v1.4557 RPL36 Bryony Thompson gene: RPL36 was added
gene: RPL36 was added to Mendeliome. Sources: Expert Review Amber,Curated sources
Mode of inheritance for gene: RPL36 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL36 were set to 28297620; 19061985; 39923319
Phenotypes for gene: RPL36 were set to Osteosarcoma, soft tissue sarcomas; Diamond Blackfan Anemia; MDS, AML; Class: BM failure syndrome (typ AR); Diamond-Blackfan anemia MONDO:0015253
Diamond Blackfan anaemia v1.16 Bryony Thompson Copied gene RPL36 from panel Haematological malignancies
Diamond Blackfan anaemia v1.16 RPL36 Bryony Thompson gene: RPL36 was added
gene: RPL36 was added to Diamond Blackfan anaemia. Sources: Expert Review Amber,Curated sources
Mode of inheritance for gene: RPL36 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL36 were set to 28297620; 19061985; 39923319
Phenotypes for gene: RPL36 were set to Osteosarcoma, soft tissue sarcomas; Diamond Blackfan Anemia; MDS, AML; Class: BM failure syndrome (typ AR); Diamond-Blackfan anemia MONDO:0015253
Bone Marrow Failure v1.141 MDM4 Zornitza Stark Phenotypes for gene: MDM4 were changed from bone marrow failure syndrome MONDO:0000159, MDM4-related to bone marrow failure syndrome 6, MONDO:0030015
Bone Marrow Failure v1.140 MDM4 Zornitza Stark Classified gene: MDM4 as Green List (high evidence)
Bone Marrow Failure v1.140 MDM4 Zornitza Stark Gene: mdm4 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.139 MDM4 Zornitza Stark reviewed gene: MDM4: Rating: GREEN; Mode of pathogenicity: None; Publications: 41758987; Phenotypes: bone marrow failure syndrome 6, MONDO:0030015; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4556 MDM4 Zornitza Stark Phenotypes for gene: MDM4 were changed from bone marrow failure syndrome MONDO:0000159, MDM4-related to bone marrow failure syndrome 6, MONDO:0030015
Mendeliome v1.4555 MDM4 Zornitza Stark Publications for gene: MDM4 were set to 32300648; 33104793
Mendeliome v1.4554 MDM4 Zornitza Stark Classified gene: MDM4 as Green List (high evidence)
Mendeliome v1.4554 MDM4 Zornitza Stark Gene: mdm4 has been classified as Green List (High Evidence).
Mendeliome v1.4553 MDM4 Zornitza Stark reviewed gene: MDM4: Rating: GREEN; Mode of pathogenicity: None; Publications: 41758987, 32300648; Phenotypes: bone marrow failure syndrome 6, MONDO:0030015; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.701 VWA3B Zornitza Stark Marked gene: VWA3B as ready
Intellectual disability syndromic and non-syndromic v1.701 VWA3B Zornitza Stark Gene: vwa3b has been classified as Green List (High Evidence).
Ataxia v1.194 VWA3B Zornitza Stark Marked gene: VWA3B as ready
Ataxia v1.194 VWA3B Zornitza Stark Gene: vwa3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.701 Zornitza Stark Copied gene VWA3B from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.701 VWA3B Zornitza Stark gene: VWA3B was added
gene: VWA3B was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA3B were set to 26157035; 41673450; 37772257
Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Ataxia v1.194 VWA3B Zornitza Stark Phenotypes for gene: VWA3B were changed from ?Spinocerebellar ataxia, autosomal recessive 22 to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Ataxia v1.193 VWA3B Zornitza Stark Classified gene: VWA3B as Green List (high evidence)
Ataxia v1.193 VWA3B Zornitza Stark Gene: vwa3b has been classified as Green List (High Evidence).
Ataxia v1.192 VWA3B Zornitza Stark reviewed gene: VWA3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 41673450, 37772257, 26157035; Phenotypes: Spinocerebellar ataxia, autosomal recessive 22, MIM# 616948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4553 VWA3B Zornitza Stark Publications for gene: VWA3B were set to 26157035
Mendeliome v1.4552 VWA3B Zornitza Stark Classified gene: VWA3B as Green List (high evidence)
Mendeliome v1.4552 VWA3B Zornitza Stark Gene: vwa3b has been classified as Green List (High Evidence).
Mendeliome v1.4551 VWA3B Zornitza Stark reviewed gene: VWA3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 41673450, 37772257, 26157035; Phenotypes: Spinocerebellar ataxia, autosomal recessive 22, MIM# 616948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.61 MYOM1 Zornitza Stark Marked gene: MYOM1 as ready
Dilated Cardiomyopathy v1.61 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.61 MYOM1 Zornitza Stark Phenotypes for gene: MYOM1 were changed from Dilated cardiomyopathy, MONDO:0005021, MYOM1-related; Hypertrophic cardiomyopathy, MONDO:0005045 to Dilated cardiomyopathy, MONDO:0005021, MYOM1-related
Dilated Cardiomyopathy v1.60 MYOM1 Zornitza Stark Deleted their comment
Dilated Cardiomyopathy v1.60 Zornitza Stark Copied gene MYOM1 from panel Mendeliome
Dilated Cardiomyopathy v1.60 MYOM1 Zornitza Stark gene: MYOM1 was added
gene: MYOM1 was added to Dilated Cardiomyopathy. Sources: Expert Review Amber,Victorian Clinical Genetics Services
disputed tags were added to gene: MYOM1.
Mode of inheritance for gene: MYOM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYOM1 were set to 27600940; 26656175; 21256114
Phenotypes for gene: MYOM1 were set to Dilated cardiomyopathy, MONDO:0005021, MYOM1-related; Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.4551 MYOM1 Zornitza Stark Phenotypes for gene: MYOM1 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Dilated cardiomyopathy, MONDO:0005021, MYOM1-related; Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.4550 MYOM1 Zornitza Stark Classified gene: MYOM1 as Amber List (moderate evidence)
Mendeliome v1.4550 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4549 MYOM1 Zornitza Stark changed review comment from: PMID 41702018 reports 28 unrelated families with heterozygous loss‑of‑function MYOM1 variants associated dilated cardiomyopathy. Individuals identified from UK Biobank, hence limited clinical and segregation data. Mouse Myom1 knock‑down functional validation; to: PMID 41702018 reports 28 unrelated families with heterozygous loss‑of‑function MYOM1 variants associated dilated cardiomyopathy. Individuals identified from UK Biobank, hence limited clinical and segregation data. Mouse Myom1 knock‑down functional validation

Note DISPUTED association with HCM.
Mendeliome v1.4549 MYOM1 Zornitza Stark edited their review of gene: MYOM1: Added comment: PMID 41702018 reports 28 unrelated families with heterozygous loss‑of‑function MYOM1 variants associated dilated cardiomyopathy. Individuals identified from UK Biobank, hence limited clinical and segregation data. Mouse Myom1 knock‑down functional validation; Changed rating: AMBER; Changed publications: 41702018, 26036949; Changed phenotypes: Dilated cardiomyopathy, MONDO:0005021, MYOM1-related
Severe early-onset obesity v1.29 BDNF Zornitza Stark Marked gene: BDNF as ready
Severe early-onset obesity v1.29 BDNF Zornitza Stark Gene: bdnf has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v1.29 BDNF Zornitza Stark Deleted their comment
Mendeliome v1.4549 BDNF Zornitza Stark changed review comment from: Refuted gene, disease association has been removed in OMIM.; to: Refuted gene, disease association with central hypoventilation has been removed in OMIM.
Severe early-onset obesity v1.29 Zornitza Stark Copied gene BDNF from panel Mendeliome
Severe early-onset obesity v1.29 BDNF Zornitza Stark gene: BDNF was added
gene: BDNF was added to Severe early-onset obesity. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: BDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BDNF were set to 41680086; 37329217; 33442278; 32493978; 30926952; 28397838
Phenotypes for gene: BDNF were set to Obesity disorder, MONDO:0011122, BDNF-related
Mendeliome v1.4549 BDNF Zornitza Stark Phenotypes for gene: BDNF were changed from to Obesity disorder, MONDO:0011122, BDNF-related
Mendeliome v1.4548 BDNF Zornitza Stark Publications for gene: BDNF were set to
Mendeliome v1.4547 BDNF Zornitza Stark Mode of inheritance for gene: BDNF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4546 BDNF Zornitza Stark Classified gene: BDNF as Amber List (moderate evidence)
Mendeliome v1.4546 BDNF Zornitza Stark Gene: bdnf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4545 BDNF Zornitza Stark edited their review of gene: BDNF: Added comment: 9 families with heterozygous variants causing severe early‑onset obesity, often with hyperphagia and neuro‑behavioral features) reported across multiple papers. Variants are generally missense with little supporting data. The PMID 32493978 report provides the first experimental functional validation (cell‑based assays showing impaired pro‑BDNF processing and loss‑of‑function).; Changed rating: AMBER; Changed publications: 41680086, 37329217, 33442278, 32493978, 30926952, 28397838; Changed phenotypes: Obesity disorder, MONDO:0011122, BDNF-related
Retinitis pigmentosa v0.243 ZNF124 Zornitza Stark Marked gene: ZNF124 as ready
Retinitis pigmentosa v0.243 ZNF124 Zornitza Stark Gene: znf124 has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.243 Zornitza Stark Copied gene ZNF124 from panel Mendeliome
Retinitis pigmentosa v0.243 ZNF124 Zornitza Stark gene: ZNF124 was added
gene: ZNF124 was added to Retinitis pigmentosa. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ZNF124 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF124 were set to 41708596
Phenotypes for gene: ZNF124 were set to Retinitis pigmentosa, MONDO:0019200, ZNF124-related
Mendeliome v1.4545 ZNF124 Zornitza Stark Marked gene: ZNF124 as ready
Mendeliome v1.4545 ZNF124 Zornitza Stark Gene: znf124 has been classified as Red List (Low Evidence).
Mendeliome v1.4545 ZNF124 Zornitza Stark gene: ZNF124 was added
gene: ZNF124 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF124 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF124 were set to 41708596
Phenotypes for gene: ZNF124 were set to Retinitis pigmentosa, MONDO:0019200, ZNF124-related
Review for gene: ZNF124 was set to RED
Added comment: PMID 41708596 report 2 individuals from a consanguineous family with retinitis pigmentosa and a homozygous splice‑site loss‑of‑function variant c.219‑1delG in ZNF124. The variant co‑segregates with disease and mouse retina‑specific knockout recapitulates the retinal degeneration phenotype through loss of ZNF124‑mediated activation of MSX2.
Sources: Literature
Fetal anomalies v1.543 CCDC57 Zornitza Stark Marked gene: CCDC57 as ready
Fetal anomalies v1.543 CCDC57 Zornitza Stark Gene: ccdc57 has been classified as Red List (Low Evidence).
Heterotaxy v1.45 CCDC57 Zornitza Stark Marked gene: CCDC57 as ready
Heterotaxy v1.45 CCDC57 Zornitza Stark Gene: ccdc57 has been classified as Red List (Low Evidence).
Heterotaxy v1.45 Zornitza Stark Copied gene CCDC57 from panel Mendeliome
Heterotaxy v1.45 CCDC57 Zornitza Stark gene: CCDC57 was added
gene: CCDC57 was added to Heterotaxy. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CCDC57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC57 were set to 41758249
Phenotypes for gene: CCDC57 were set to Visceral heterotaxy, MONDO:0018677, CCDC57-related
Fetal anomalies v1.543 Zornitza Stark Copied gene CCDC57 from panel Mendeliome
Fetal anomalies v1.543 CCDC57 Zornitza Stark gene: CCDC57 was added
gene: CCDC57 was added to Fetal anomalies. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CCDC57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC57 were set to 41758249
Phenotypes for gene: CCDC57 were set to Visceral heterotaxy, MONDO:0018677, CCDC57-related
Mendeliome v1.4544 CCDC57 Zornitza Stark Marked gene: CCDC57 as ready
Mendeliome v1.4544 CCDC57 Zornitza Stark Gene: ccdc57 has been classified as Red List (Low Evidence).
Mendeliome v1.4544 CCDC57 Zornitza Stark gene: CCDC57 was added
gene: CCDC57 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC57 were set to 41758249
Phenotypes for gene: CCDC57 were set to Visceral heterotaxy, MONDO:0018677, CCDC57-related
Review for gene: CCDC57 was set to RED
Added comment: PMID 41758249 reports a single individual with compound heterozygous missense variants presenting with isolated laterality disorder (situs inversus, dextrocardia, chronic sinusitis). Xenopus rescue experiments showed that wild‑type CCDC57 mRNA rescues ciliary structure and fluid flow, whereas patient variant mRNAs fail to rescue, supporting loss‑of‑function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.700 XPOT Zornitza Stark Marked gene: XPOT as ready
Intellectual disability syndromic and non-syndromic v1.700 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.333 XPOT Zornitza Stark Marked gene: XPOT as ready
Deafness_IsolatedAndComplex v1.333 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v1.10 XPOT Zornitza Stark Marked gene: XPOT as ready
Pulmonary Fibrosis_Interstitial Lung Disease v1.10 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Mendeliome v1.4543 ICOSLG Sangavi Sivagnanasundram reviewed gene: ICOSLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 34694545; Phenotypes: immunodeficiency 119, MONDO:0970993; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4543 GSX2 Sangavi Sivagnanasundram reviewed gene: GSX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39119454; Phenotypes: diencephalic-mesencephalic junction dysplasia syndrome 2, MONDO:0020762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v1.10 Zornitza Stark Copied gene XPOT from panel Mendeliome
Pulmonary Fibrosis_Interstitial Lung Disease v1.10 XPOT Zornitza Stark gene: XPOT was added
gene: XPOT was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Green,Literature
preprint tags were added to gene: XPOT.
Mode of inheritance for gene: XPOT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPOT were set to 10.64898/2026.01.28.26344748
Phenotypes for gene: XPOT were set to Syndromic disease, MONDO:0002254
Intellectual disability syndromic and non-syndromic v1.700 Zornitza Stark Copied gene XPOT from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.700 XPOT Zornitza Stark gene: XPOT was added
gene: XPOT was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
preprint tags were added to gene: XPOT.
Mode of inheritance for gene: XPOT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPOT were set to 10.64898/2026.01.28.26344748
Phenotypes for gene: XPOT were set to Syndromic disease, MONDO:0002254
Deafness_IsolatedAndComplex v1.333 Zornitza Stark Copied gene XPOT from panel Mendeliome
Deafness_IsolatedAndComplex v1.333 XPOT Zornitza Stark gene: XPOT was added
gene: XPOT was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
preprint tags were added to gene: XPOT.
Mode of inheritance for gene: XPOT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPOT were set to 10.64898/2026.01.28.26344748
Phenotypes for gene: XPOT were set to Syndromic disease, MONDO:0002254
Mendeliome v1.4543 XPOT Zornitza Stark Marked gene: XPOT as ready
Mendeliome v1.4543 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Mendeliome v1.4543 XPOT Zornitza Stark Classified gene: XPOT as Green List (high evidence)
Mendeliome v1.4543 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Mendeliome v1.4542 XPOT Zornitza Stark gene: XPOT was added
gene: XPOT was added to Mendeliome. Sources: Literature
preprint tags were added to gene: XPOT.
Mode of inheritance for gene: XPOT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPOT were set to 10.64898/2026.01.28.26344748
Phenotypes for gene: XPOT were set to Syndromic disease, MONDO:0002254
Review for gene: XPOT was set to GREEN
Added comment: Preprint by Von Hardenberg et al 2026 reports 8 individuals from 5 unrelated families with biallelic loss‑of‑function XPOT variants presenting with childhood‑onset severe sensorineural hearing loss, recurrent infections/bronchiectasis, developmental delay and growth retardation. Functional studies show absent XPOT protein in patient fibroblasts, reduced TNF‑α translation, and xpot‑deficient zebrafish recapitulating the multisystem phenotype.

All reported variants are homozygous.
Sources: Literature
Cardiomyopathy_Paediatric v0.224 WDR59 Zornitza Stark Marked gene: WDR59 as ready
Cardiomyopathy_Paediatric v0.224 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.699 WDR59 Zornitza Stark Marked gene: WDR59 as ready
Intellectual disability syndromic and non-syndromic v1.699 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Cataract v0.631 WDR59 Zornitza Stark Marked gene: WDR59 as ready
Cataract v0.631 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.38 TTN Zornitza Stark edited their review of gene: TTN: Added comment: No evidence for association with rhabdomyolysis.; Changed rating: RED; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.59 CAP2 Elena Savva reviewed gene: CAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22945801; Phenotypes: Cardiomyopathy, dilated, 2I MIM#620462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.126 OTUD3 Peter McNaughton gene: OTUD3 was added
gene: OTUD3 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: OTUD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OTUD3 were set to PMID: 41067575
Phenotypes for gene: OTUD3 were set to Ulcerative colitis
Review for gene: OTUD3 was set to AMBER
Added comment: Multigenerational family with a medically refractory colitis phenotype permitted identification of the A143T missense mutation in OTUD3 as the causal variant. Murine model replicating phenotype and demonstrating impaired intestinal barrier function.
Amber for single kindred.
Sources: Literature
Autoinflammatory Disorders v2.46 Chirag Patel Copied gene CTLA4 from panel Disorders of immune dysregulation
Autoinflammatory Disorders v2.46 CTLA4 Chirag Patel gene: CTLA4 was added
gene: CTLA4 was added to Autoinflammatory Disorders. Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: CTLA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTLA4 were set to 25213377; 25329329; 30377434
Phenotypes for gene: CTLA4 were set to Autoimmune lymphoproliferative syndrome, type V, MIM# 616100
Autoinflammatory Disorders v2.46 CTLA4 Chirag Patel Marked gene: CTLA4 as ready
Autoinflammatory Disorders v2.46 CTLA4 Chirag Patel Gene: ctla4 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v2.46 Chirag Patel Copied gene CTLA4 from panel Autoimmune Lymphoproliferative Syndrome
Autoinflammatory Disorders v2.46 CTLA4 Chirag Patel gene: CTLA4 was added
gene: CTLA4 was added to Autoinflammatory Disorders. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CTLA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTLA4 were set to 39060684; 38302222
Phenotypes for gene: CTLA4 were set to Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation MIM#616100; autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency MONDO:0014493
Mendeliome v1.4541 PLEKHA7 Lucy Spencer Phenotypes for gene: PLEKHA7 were changed from Cleft lip and palate to Cleft lip/palate MONDO:0016044, PLEKHA7-related
Atrial Fibrillation v1.7 MYL4 Zornitza Stark Marked gene: MYL4 as ready
Atrial Fibrillation v1.7 MYL4 Zornitza Stark Gene: myl4 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v1.7 NUP155 Zornitza Stark Marked gene: NUP155 as ready
Atrial Fibrillation v1.7 NUP155 Zornitza Stark Gene: nup155 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.699 Zornitza Stark Copied gene WDR59 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.699 WDR59 Zornitza Stark gene: WDR59 was added
gene: WDR59 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
founder tags were added to gene: WDR59.
Mode of inheritance for gene: WDR59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR59 were set to 41715954
Phenotypes for gene: WDR59 were set to Syndromic disease, MONDO:0002254
Cataract v0.631 Zornitza Stark Copied gene WDR59 from panel Mendeliome
Cataract v0.631 WDR59 Zornitza Stark gene: WDR59 was added
gene: WDR59 was added to Cataract. Sources: Expert Review Amber,Literature
founder tags were added to gene: WDR59.
Mode of inheritance for gene: WDR59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR59 were set to 41715954
Phenotypes for gene: WDR59 were set to Syndromic disease, MONDO:0002254
Cardiomyopathy_Paediatric v0.224 Zornitza Stark Copied gene WDR59 from panel Mendeliome
Cardiomyopathy_Paediatric v0.224 WDR59 Zornitza Stark gene: WDR59 was added
gene: WDR59 was added to Cardiomyopathy_Paediatric. Sources: Expert Review Amber,Literature
founder tags were added to gene: WDR59.
Mode of inheritance for gene: WDR59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR59 were set to 41715954
Phenotypes for gene: WDR59 were set to Syndromic disease, MONDO:0002254
Mendeliome v1.4540 WDR59 Zornitza Stark Marked gene: WDR59 as ready
Mendeliome v1.4540 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4540 WDR59 Zornitza Stark Classified gene: WDR59 as Amber List (moderate evidence)
Mendeliome v1.4540 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4539 WDR59 Zornitza Stark gene: WDR59 was added
gene: WDR59 was added to Mendeliome. Sources: Literature
founder tags were added to gene: WDR59.
Mode of inheritance for gene: WDR59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR59 were set to 41715954
Phenotypes for gene: WDR59 were set to Syndromic disease, MONDO:0002254
Review for gene: WDR59 was set to AMBER
Added comment: PMID 41715954 reports six individuals from four unrelated families with biallelic WDR59 variants causing early‑onset autosomal recessive syndromic dilated cardiomyopathy, cataract, facial dysmorphism, growth retardation and developmental delay. Three Saudi families share the homozygous missense founder variant c.2887G>A (p.Gly963Arg) and a French family carries compound heterozygous intronic splice‑site variants; RNA‑seq shows aberrant splicing and reduced WDR59 expression, supporting loss‑of‑function. Segregation data confirm recessive inheritance, making WDR59 a diagnostic‑grade gene.

Founder variant accounts for three of four families, hence Amber rating
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.698 WAPL Zornitza Stark Marked gene: WAPL as ready
Intellectual disability syndromic and non-syndromic v1.698 WAPL Zornitza Stark Gene: wapl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.698 Zornitza Stark Copied gene WAPL from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.698 WAPL Zornitza Stark gene: WAPL was added
gene: WAPL was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
preprint tags were added to gene: WAPL.
Mode of inheritance for gene: WAPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WAPL were set to 10.64898/2026.02.23.26346364; 30158690
Phenotypes for gene: WAPL were set to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.4538 WAPL Zornitza Stark Marked gene: WAPL as ready
Mendeliome v1.4538 WAPL Zornitza Stark Gene: wapl has been classified as Green List (High Evidence).
Mendeliome v1.4538 WAPL Zornitza Stark Classified gene: WAPL as Green List (high evidence)
Mendeliome v1.4538 WAPL Zornitza Stark Gene: wapl has been classified as Green List (High Evidence).
Mendeliome v1.4537 WAPL Zornitza Stark gene: WAPL was added
gene: WAPL was added to Mendeliome. Sources: Literature
preprint tags were added to gene: WAPL.
Mode of inheritance for gene: WAPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WAPL were set to 10.64898/2026.02.23.26346364; 30158690
Phenotypes for gene: WAPL were set to complex neurodevelopmental disorder, MONDO:0100038
Review for gene: WAPL was set to GREEN
Added comment: PMID 30158690 reports a single de novo missense WAPL variant in a patient with mild CdLS‑like cohesinopathy, while a preprint (Boone et al 2026) describes 27 unrelated individuals with heterozygous loss‑of‑function or damaging missense WAPL variants presenting with a neurodevelopmental syndrome (developmental delay/intellectual disability, facial dysmorphism, congenital anomalies such as clubfoot). Combined, the two studies provide 28 unrelated families supporting WAPL haploinsufficiency as a cause of a complex neurodevelopmental disorder, with mouse and iPSC functional data corroborating pathogenicity.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.127 TFDP3 Zornitza Stark Marked gene: TFDP3 as ready
Infertility and Recurrent Pregnancy Loss v1.127 TFDP3 Zornitza Stark Gene: tfdp3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.127 Zornitza Stark Copied gene TFDP3 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.127 TFDP3 Zornitza Stark gene: TFDP3 was added
gene: TFDP3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TFDP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TFDP3 were set to 41634254
Phenotypes for gene: TFDP3 were set to Infertility disorder, MONDO:0005047, TFDP3-related
Mendeliome v1.4536 TFDP3 Zornitza Stark Marked gene: TFDP3 as ready
Mendeliome v1.4536 TFDP3 Zornitza Stark Gene: tfdp3 has been classified as Green List (High Evidence).
Mendeliome v1.4536 TFDP3 Zornitza Stark Classified gene: TFDP3 as Green List (high evidence)
Mendeliome v1.4536 TFDP3 Zornitza Stark Gene: tfdp3 has been classified as Green List (High Evidence).
Mendeliome v1.4535 TFDP3 Zornitza Stark gene: TFDP3 was added
gene: TFDP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TFDP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TFDP3 were set to 41634254
Phenotypes for gene: TFDP3 were set to Infertility disorder, MONDO:0005047, TFDP3-related
Review for gene: TFDP3 was set to GREEN
Added comment: PMID 41634254 reports 8 individuals from 7 families with X‑linked hemizygous TFDP3 loss‑of‑function variants presenting with severe oligoasthenoteratozoospermia. Affected males have dramatically reduced sperm concentration, motility, and abnormal morphology. Functional studies show reduced TFDP3 protein in patient sperm and recapitulation of the infertility phenotype in TFDP3 knock‑down cynomolgus monkeys with increased E2F1‑mediated apoptosis.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v1.9 RPA2 Zornitza Stark Marked gene: RPA2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v1.9 RPA2 Zornitza Stark Gene: rpa2 has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.139 RPA2 Zornitza Stark Marked gene: RPA2 as ready
Bone Marrow Failure v1.139 RPA2 Zornitza Stark Gene: rpa2 has been classified as Red List (Low Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v1.9 Zornitza Stark Copied gene RPA2 from panel Mendeliome
Pulmonary Fibrosis_Interstitial Lung Disease v1.9 RPA2 Zornitza Stark gene: RPA2 was added
gene: RPA2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RPA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RPA2 were set to 41703052; 39231615
Phenotypes for gene: RPA2 were set to Telomere syndrome, MONDO:0100137, RPA2-related
Bone Marrow Failure v1.139 Zornitza Stark Copied gene RPA2 from panel Mendeliome
Bone Marrow Failure v1.139 RPA2 Zornitza Stark gene: RPA2 was added
gene: RPA2 was added to Bone Marrow Failure. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RPA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RPA2 were set to 41703052; 39231615
Phenotypes for gene: RPA2 were set to Telomere syndrome, MONDO:0100137, RPA2-related
Mendeliome v1.4534 RPA2 Zornitza Stark Marked gene: RPA2 as ready
Mendeliome v1.4534 RPA2 Zornitza Stark Gene: rpa2 has been classified as Red List (Low Evidence).
Mendeliome v1.4534 RPA2 Zornitza Stark gene: RPA2 was added
gene: RPA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RPA2 were set to 41703052; 39231615
Phenotypes for gene: RPA2 were set to Telomere syndrome, MONDO:0100137, RPA2-related
Review for gene: RPA2 was set to RED
Added comment: PMID 41703052 reports a 6‑year‑old individual from a consanguineous family who is homozygous for the splice‑site variant c.409‑2A>G (p.Q136_K138del). The patient presented with early‑onset bone‑marrow failure, immunodeficiency, microcephaly, dysmorphic features and severely short telomeres. The heterozygous parents are asymptomatic carriers. Functional studies showed ~50% reduction of RPA2 protein, destabilization of the OB‑fold ssDNA‑binding groove, impaired telomere binding, severe telomere shortening, increased telomere variant repeats and chromosome end‑to‑end fusions, supporting a loss‑of‑function mechanism.

PMID 39231615 reports 2 individuals from 2 unrelated families with a heterozygous missense variant c.767A>G (p.Y256C) presenting with adult‑onset telomere biology disorder characterized by pleuroparenchymal fibroelastosis/interstitial lung disease, short telomeres, bone‑marrow failure (macrocytic anemia, myelodysplastic syndrome), liver disease and osteoporosis. Variant is ultra‑rare (gnomAD v4 1 het) and predicted deleterious. Functional studies (RPE1 knock‑in cell lines, RFWD3 interaction and ubiquitination assays, ATR signaling, telomere length assays, and a mouse model lethal in homozygous state) demonstrate loss‑of‑function effects, supporting pathogenicity. Both patients acquired, in a subset of blood cells, somatic genetic rescue events in either POT1 genes or TERT promoters known to counteract the accelerated telomere shortening.
Sources: Literature
Ataxia v1.192 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Ataxia v1.192 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.697 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Intellectual disability syndromic and non-syndromic v1.697 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v1.16 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Mitochondrial disease v1.16 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.384 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Genetic Epilepsy v1.384 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.126 RAD51AP2 Zornitza Stark Marked gene: RAD51AP2 as ready
Infertility and Recurrent Pregnancy Loss v1.126 RAD51AP2 Zornitza Stark Gene: rad51ap2 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.126 Zornitza Stark Copied gene RAD51AP2 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.126 RAD51AP2 Zornitza Stark gene: RAD51AP2 was added
gene: RAD51AP2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RAD51AP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD51AP2 were set to 41644825; 36153927
Phenotypes for gene: RAD51AP2 were set to Infertility disorder, MONDO:0005047, RAD51AP2-related
Mendeliome v1.4533 RAD51AP2 Zornitza Stark Marked gene: RAD51AP2 as ready
Mendeliome v1.4533 RAD51AP2 Zornitza Stark Gene: rad51ap2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4533 RAD51AP2 Zornitza Stark Classified gene: RAD51AP2 as Amber List (moderate evidence)
Mendeliome v1.4533 RAD51AP2 Zornitza Stark Gene: rad51ap2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v1.16 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Mitochondrial disease v1.16 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Mitochondrial disease. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Mendeliome v1.4532 RAD51AP2 Zornitza Stark gene: RAD51AP2 was added
gene: RAD51AP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAD51AP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD51AP2 were set to 41644825; 36153927
Phenotypes for gene: RAD51AP2 were set to Infertility disorder, MONDO:0005047, RAD51AP2-related
Review for gene: RAD51AP2 was set to AMBER
Added comment: PMID 41644825 reports one male patient from a Turkish consanguineous family and PMID 36153927 reports two brothers from an unrelated family; together three individuals from two unrelated families carry biallelic loss‑of‑function RAD51AP2 variants and present with non‑obstructive azoospermia and meiotic arrest. Both studies demonstrate autosomal recessive inheritance, and a mouse Rad51ap2 knockout recapitulates the infertility phenotype, providing functional support for causality.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.697 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.697 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Genetic Epilepsy v1.384 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Genetic Epilepsy v1.384 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Genetic Epilepsy. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Infertility and Recurrent Pregnancy Loss v1.125 Zornitza Stark removed gene:C17orf80 from the panel
Ataxia v1.192 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Ataxia v1.192 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Ataxia. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Infertility and Recurrent Pregnancy Loss v1.124 PIWIL1 Zornitza Stark Marked gene: PIWIL1 as ready
Infertility and Recurrent Pregnancy Loss v1.124 PIWIL1 Zornitza Stark Gene: piwil1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.124 Zornitza Stark Copied gene PIWIL1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.124 PIWIL1 Zornitza Stark gene: PIWIL1 was added
gene: PIWIL1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PIWIL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PIWIL1 were set to 41706354; 39122675; 37335463; 36379263; 33877510; 28552346
Phenotypes for gene: PIWIL1 were set to Infertility disorder, MONDO:0005047, PIWIL1-related
Mendeliome v1.4531 PIWIL1 Zornitza Stark Marked gene: PIWIL1 as ready
Mendeliome v1.4531 PIWIL1 Zornitza Stark Gene: piwil1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4531 PIWIL1 Zornitza Stark Classified gene: PIWIL1 as Amber List (moderate evidence)
Mendeliome v1.4531 PIWIL1 Zornitza Stark Gene: piwil1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4530 PIWIL1 Zornitza Stark gene: PIWIL1 was added
gene: PIWIL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIWIL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PIWIL1 were set to 41706354; 39122675; 37335463; 36379263; 33877510; 28552346
Phenotypes for gene: PIWIL1 were set to Infertility disorder, MONDO:0005047, PIWIL1-related
Review for gene: PIWIL1 was set to AMBER
Added comment: PMID 28552346 reports three unrelated families with heterozygous PIWIL1 missense variants causing idiopathic azoospermia; mouse knock‑in and rescue experiments provide functional support. PMID 41706354 and PMID 39122675 describe two unrelated families with recessive loss‑of‑function PIWIL1 frameshift/stop‑gain variants leading to non‑obstructive azoospermia and spermatogenic arrest, confirmed by immunohistochemistry and piRNA profiling. PMID 37335463 identifies a compound‑heterozygous patient and four heterozygous carriers of rare missense/truncating PIWIL1 variants, and a Miwi R371W knock‑in mouse recapitulates subfertility.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.123 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready