ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1957_1960dup (p.Met654fs)

dbSNP: rs63751167
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074699 SCV000107904 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Labcorp Genetics (formerly Invitae), Labcorp RCV001060756 SCV001225466 pathogenic Hereditary nonpolyposis colorectal neoplasms 2024-07-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met654Serfs*8) 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: 14574004). ClinVar contains an entry for this variant (Variation ID: 89235). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV001191931 SCV001359869 pathogenic Hereditary cancer-predisposing syndrome 2020-05-27 criteria provided, single submitter clinical testing This variant inserts 4 nucleotides in exon 4 of the MSH6 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with colorectal cancer (PMID: 14574004). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Myriad Genetics, Inc. RCV003450936 SCV004185781 pathogenic Lynch syndrome 5 2023-08-16 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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