ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1293dup (p.Leu432fs)

dbSNP: rs1553361162
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000608554 SCV000731562 pathogenic Lynch syndrome 2017-06-30 criteria provided, single submitter clinical testing The p.Leu432fs variant in MSH2 has not been previously reported in individuals w ith Lynch syndrome or in large population studies, though the ability of these s tudies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 432 and leads to a premature termination codon 11 amino acids downstrea m. This alteration is then predicted to lead to a truncated or absent protein. H eterozygous loss of function of the MSH2 gene is an established disease mechanis m in Lynch syndrome. In summary, this variant meets criteria to be classified as pathogenic for Lynch syndrome in an autosomal dominant manner based upon the pr edicted impact to the protein and absence in controls.
Invitae RCV001227883 SCV001400261 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-09-17 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has not been reported in the literature in individuals with MSH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu432Ilefs*11) in the MSH2 gene. It is expected to result in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV003451453 SCV004187984 pathogenic Lynch syndrome 1 2023-08-01 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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