ClinVar Miner

Submissions for variant NM_001849.4(COL6A2):c.1046_1053+1del

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003014190 SCV003317203 uncertain significance Bethlem myopathy 1A 2022-10-28 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as c.1046_1053+1del. This variant has been observed in individual(s) with clinical features of autosomal dominant COL6A2-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This variant, c.1045_1053del, results in the deletion of 3 amino acid(s) of the COL6A2 protein (p.Asn350_Gly352del), but otherwise preserves the integrity of the reading frame. This variant also falls at the last nucleotide of exon 11, which is part of the consensus splice site for this exon.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.