Submissions for variant NC_000003.11:g.(?_48605912)_(48607368_?)del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV004582238	SCV005066361	pathogenic	not provided	2023-02-04	criteria provided, single submitter	clinical testing	This variant is a gross deletion of the genomic region encompassing exon(s) 99-104 of the COL7A1 gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with COL7A1-related conditions. 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.Gly2575Arg amino acid residue in COL7A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8592061, 16971478, 18450758). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.