ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.999del (p.Lys334fs)

dbSNP: rs1060502932
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002230123 SCV000551242 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-05-02 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: 410503). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys334Argfs*4) 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).
GeneDx RCV000522846 SCV000618302 pathogenic not provided 2017-02-27 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH6 is denoted c.999delC at the cDNA level and p.Lys334ArgfsX4 (K334RfsX4) at the protein level. The normal sequence, with the base that is deleted in brackets, is AAAC[delC]AAGA. The deletion causes a frameshift which changes a Lysine to an Arginine at codon 334, and creates a premature stop codon at position 4 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Myriad Genetics, Inc. RCV003449151 SCV004185634 pathogenic Lynch syndrome 5 2023-08-11 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 RCV004568056 SCV005054861 likely pathogenic Endometrial carcinoma 2024-03-09 criteria provided, single submitter clinical testing

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