Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003029062 | SCV003315586 | likely pathogenic | Cataract 1 multiple types | 2023-03-01 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 2103996). This missense change has been observed in individual(s) with congenital cataracts (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 46 of the GJA8 protein (p.Gly46Glu). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly46 amino acid residue in GJA8. Other variant(s) that disrupt this residue have been observed in individuals with GJA8-related conditions (PMID: 19684000, 21686328), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects GJA8 function (PMID: 25260631). |
| The Key Laboratory for Human Disease Gene Study of Sichuan Province, |
RCV003388141 | SCV003920679 | likely pathogenic | acorea,microphthalmia and cataract syndrome | no assertion criteria provided | research | It provides a new screening target for prenatal diagnosis of familial acorea， microphthalmia and cataract syndrome |