Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000337509 | SCV000336064 | pathogenic | not provided | 2017-08-31 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000337509 | SCV002019663 | pathogenic | not provided | 2019-08-31 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002518892 | SCV003444400 | pathogenic | Bethlem myopathy 1A | 2025-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 301 of the COL6A2 protein (p.Gly301Ser). 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 COL6A2-related conditions (PMID: 24271325, 30564623). ClinVar contains an entry for this variant (Variation ID: 283758). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the triple helix domain of COL6A2. 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). In COL6A2, missense variants at these glycine residues are significantly enriched in individuals with autosomal dominant disease (PMID: 15689448, 24038877) compared to the general population (ExAC). This variant disrupts the p.Gly301 amino acid residue in COL6A2. Other variant(s) that disrupt this residue have been observed in individuals with COL6A2-related conditions (PMID: 17785673, 24271325), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |