ClinVar Miner

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

dbSNP: rs267608041
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae 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

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