Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000707815 | SCV000836925 | pathogenic | Bethlem myopathy 1 | 2021-08-13 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 16-21 of the COL6A3 gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. A similar copy number variant has been observed in individual(s) with clinical features of COL6A3-related conditions (Invitae). This variant disrupts the triple helix domain of COL6A3. 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 COL6A3, missense variants at these glycine residues are significantly enriched in individuals with autosomal dominant disease (PMID: 15689448, 24038877) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic. |