ClinVar Miner

Submissions for variant NM_005267.5(GJA8):c.226C>T (p.Arg76Cys)

dbSNP: rs1553242577
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001941871 SCV002234787 pathogenic Cataract 1 multiple types 2023-05-23 criteria provided, single submitter clinical testing This variant disrupts the p.Arg76 amino acid residue in GJA8. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27216975, 30928190). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJA8 protein function. ClinVar contains an entry for this variant (Variation ID: 1454428). This missense change has been observed in individuals with autosomal dominant congenital cataracts (PMID: 23508780; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 76 of the GJA8 protein (p.Arg76Cys). For these reasons, this variant has been classified as Pathogenic.

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