ClinVar Miner

Submissions for variant NM_001848.3(COL6A1):c.1056+1G>C

dbSNP: rs398123631
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV001780557 SCV002017477 pathogenic not provided 2019-07-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002541114 SCV003461977 pathogenic Bethlem myopathy 1A 2025-01-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 14 of the COL6A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL6A1 are known to be disease-causing for autosomal recessive COL6A1-related conditions (PMID: 21280092, 20976770). However, certain variants affecting donor or acceptor splice sites in the triple helical domain of COL6A1 are expected to result in in-frame exon skipping and have been reported to cause autosomal dominant COL6A1-related conditions (PMID: 18366090). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of autosomal dominant COL6A1-related conditions (PMID: 25749816, 29382405). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1322138). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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.