ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.6182G>T (p.Gly2061Val)

dbSNP: rs2044208810
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biomedical Innovation Departament, CIEMAT RCV001352768 SCV001547350 pathogenic Epidermolysis bullosa dystrophica 2018-03-27 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV002547568 SCV003525226 pathogenic not provided 2022-10-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2061 of the COL7A1 protein (p.Gly2061Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal dominant epidermolysis bullosa (PMID: 20184583; Invitae). ClinVar contains an entry for this variant (Variation ID: 1047984). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65"). This variant disrupts the triple helix domain of COL7A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236), and variants at these glycine residues in COL7A1 are more frequently observed in individuals with disease than in the general population (PMID: 22058051). However, the clinical significance of this observation remains uncertain since only a limited number of affected individuals have been described to date. This variant disrupts the p.Gly2061 amino acid residue in COL7A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17282977). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
GeneDx RCV002547568 SCV005685653 pathogenic not provided 2024-07-22 criteria provided, single submitter clinical testing Previously reported in association with autosomal dominant epidermolysis bullosa (PMID: 20184583); Located in the highly conserved Gly-X-Y repeat of the collagenous domain; Glycine substitution variants in this region of the COLVII protein destabilize the collagen triple helix resulting in skin fragility due to poor anchoring of the basement membrane to the underlying dermis (PMID: 20301481); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 21448560, 20301481, 20184583)

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