ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.738_741del (p.Lys246fs)

dbSNP: rs267608041
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001214344 SCV001386021 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-05-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Lys246Asnfs*32) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 24278394). ClinVar contains an entry for this variant (Variation ID: 944031).
Ambry Genetics RCV002379810 SCV002672107 pathogenic Hereditary cancer-predisposing syndrome 2019-06-25 criteria provided, single submitter clinical testing The c.738_741delAAAA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of 4 nucleotides at nucleotide positions 738 to 741, causing a translational frameshift with a predicted alternate stop codon (p.K246Nfs*32). This alteration was detected in 1/132 unrelated individuals who met either Amsterdam I or Amsterdam II criteria (De Lellis L et al. PLoS ONE, 2013 Nov;8:e81194). 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. RCV003449676 SCV004187126 pathogenic Lynch syndrome 5 2023-08-10 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV003462724 SCV004195784 pathogenic Endometrial carcinoma 2023-05-15 criteria provided, single submitter clinical testing

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.