ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3172+1G>C

dbSNP: rs587779255
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001018969 SCV001180269 likely pathogenic Hereditary cancer-predisposing syndrome 2018-09-22 criteria provided, single submitter clinical testing The c.3172+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 4 of the MSH6 gene. This nucleotide position is highly conserved in available vertebrate species. This splice prediction software predicts that this alteration will abolish the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Color Diagnostics, LLC DBA Color Health RCV001018969 SCV001352059 likely pathogenic Hereditary cancer-predisposing syndrome 2022-06-06 criteria provided, single submitter clinical testing This variant causes a G>C nucleotide substitution at the +1 position of intron 4 of the MSH6 gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Different variants affecting the same splice donor site, c.3172+1G>A and c.3172+1G>T, are known to be disease-causing (ClinVar variation ID: 428291, 89344). Loss of MSH6 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Likely Pathogenic.
Myriad Genetics, Inc. RCV003455104 SCV004189299 likely pathogenic Lynch syndrome 5 2023-08-22 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

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.