ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.7051G>A (p.Gly2351Arg)

gnomAD frequency: 0.00001  dbSNP: rs1800013
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biomedical Innovation Departament, CIEMAT RCV001352824 SCV001547367 pathogenic Epidermolysis bullosa dystrophica 2017-10-09 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001871903 SCV002247315 pathogenic not provided 2023-11-10 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 2351 of the COL7A1 protein (p.Gly2351Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 8644730, 12485454, 21448560). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant has been reported in individual(s) with clinical features of autosomal dominant dystrophic epidermolysis bullosa (PMID: 8644730); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 1048020). 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 with a positive predictive value of 95%. 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. For these reasons, this variant has been classified as Pathogenic.
Center for Research in Genodermatoses and Epidermolysis Bullosa, University of Buenos Aires RCV002276703 SCV002499339 pathogenic Recessive dystrophic epidermolysis bullosa 2022-03-14 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.