Total submissions: 4
| 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). 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). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004799747 | SCV005422086 | pathogenic | Ullrich congenital muscular dystrophy 1A | 2024-10-25 | criteria provided, single submitter | clinical testing | Variant summary: COL6A2 c.847G>A (p.Gly283Arg) results in a non-conservative amino acid change located in the Collagen triple helix repeat (IPR008160) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249228 control chromosomes (gnomAD). c.847G>A has been reported in the literature in at least 3 heterozygous individuals affected with (or symptoms suggestive of) Ullrich congenital muscular dystrophy (e.g. Lampe_2005, Nadeau_2009, Brinas_2010, Foley_2013, and in an Internal LCA patient), and in multiple patients the variant was noted to be a de novo occurrence. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15689448, 19564581, 20976770, 24271325). ClinVar contains an entry for this variant (Variation ID: 17167). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV003764603 | SCV000038990 | pathogenic | Ullrich congenital muscular dystrophy 1B | 2009-07-07 | no assertion criteria provided | literature only |