ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.1663-1G>A

dbSNP: rs749145939
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
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001810573 SCV001474220 likely pathogenic not provided 2020-04-23 criteria provided, single submitter clinical testing The COL3A1 c.1663-1G>A variant (rs749145939), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on a single chromosome in the Genome Aggregation Database (1/251084 alleles), indicating it is not a common polymorphism. This variant abolishes the canonical splice acceptor site of intron 23, which is likely to disrupt gene function. Based on available information, this variant is considered to be likely pathogenic.
Invitae RCV001871698 SCV002295185 likely pathogenic Ehlers-Danlos syndrome, type 4 2023-11-13 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 23 of the COL3A1 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 COL3A1 are known to be pathogenic (PMID: 24922459). This variant is present in population databases (rs749145939, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 994326). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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.