Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
3billion | RCV001808307 | SCV002058986 | uncertain significance | Recessive dystrophic epidermolysis bullosa | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset (PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.9, 3CNET: 0.895, PP3_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331210 | SCV004038471 | uncertain significance | not specified | 2023-08-09 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003679075 | SCV004403397 | likely pathogenic | not provided | 2023-09-14 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Gly2372 amino acid residue in COL7A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21448560). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2372 of the COL7A1 protein (p.Gly2372Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL7A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1333619). 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 COL7A1 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. |