Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003332026 | SCV004038868 | likely pathogenic | Epidermolysis bullosa dystrophica | 2023-08-10 | criteria provided, single submitter | clinical testing | Variant summary: COL7A1 c.7580G>A (p.Gly2527Glu) results in a non-conservative amino acid change located in the Collagen triple helix repeat (IPR008160) of the encoded protein sequence. Alterations of glycine residues within the collagen triple-helix are common mechanisms of disease. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250240 control chromosomes (gnomAD). c.7580G>A has been reported in the literature in individuals affected with Dystrophic Epidermolysis Bullosa (Has_2018). This report does not provide unequivocal conclusions about association of the variant with Dystrophic Epidermolysis Bullosa. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 29242947). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV005103943 | SCV005815813 | uncertain significance | not provided | 2024-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2527 of the COL7A1 protein (p.Gly2527Glu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with autosomal dominant dystrophic epidermolysis bullosa (PMID: 29242947). ClinVar contains an entry for this variant (Variation ID: 2581621). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt COL7A1 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. |