Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000269898 | SCV000342626 | uncertain significance | not provided | 2016-06-06 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000816890 | SCV000957419 | pathogenic | Bethlem myopathy 1A | 2022-03-21 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 17167). This missense change has been observed in individual(s) with autosomal dominant Ullrich congenital muscular dystrophy (PMID: 24038877). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 283 of the COL6A2 protein (p.Gly283Arg). 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 COL6A2 protein function. For these reasons, this variant has been classified as Pathogenic. 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). |
| OMIM | RCV003764603 | SCV000038990 | pathogenic | Ullrich congenital muscular dystrophy 1B | 2009-07-07 | no assertion criteria provided | literature only |