Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003619817 | SCV004518760 | uncertain significance | Cataract 1 multiple types | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 8 of the GJA8 protein (p.Gly8Arg). This variant is present in population databases (rs202041458, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GJA8-related conditions. ClinVar contains an entry for this variant (Variation ID: 2342241). 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 with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002956000 | SCV003676286 | uncertain significance | Inborn genetic diseases | 2022-12-01 | criteria provided, single submitter | clinical testing | The c.22G>A (p.G8R) alteration is located in exon 2 (coding exon 1) of the GJA8 gene. This alteration results from a G to A substitution at nucleotide position 22, causing the glycine (G) at amino acid position 8 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |