ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1835C>A (p.Ser612Ter)

dbSNP: rs63750564
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074690 SCV000107893 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV002408572 SCV002710906 pathogenic Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing The p.S612* pathogenic mutation (also known as c.1835C>A), located in coding exon 4 of the MSH6 gene, results from a C to A substitution at nucleotide position 1835. This changes the amino acid from a serine to a stop codon within coding exon 4. This mutation has been detected in multiple Lynch syndrome patients whose tumors demonstrated microsatellite instability and/or loss of MSH6 protein expression on IHC (Okkels H et al. Int J Colorectal Dis. 2006 Dec;21(8):847-50; Klarskov L et al. Am J Surg Pathol. 2011 Sep;35(9):1391-9; Baert-Desurmont S et al. Eur J Hum Genet. 2018 Nov;26(11):1597-1602). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003450933 SCV004185745 pathogenic Lynch syndrome 5 2023-08-15 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Invitae RCV003593866 SCV004293906 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-06-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89227). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 16525781). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser612*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816).

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.