ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.901A>T (p.Lys301Ter)

dbSNP: rs63749915
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076746 SCV000107783 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV001854341 SCV002236751 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-05-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 15849733). ClinVar contains an entry for this variant (Variation ID: 91241). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys301*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).
Ambry Genetics RCV002371917 SCV002686315 pathogenic Hereditary cancer-predisposing syndrome 2021-01-21 criteria provided, single submitter clinical testing The p.K301* pathogenic mutation (also known as c.901A>T), located in coding exon 5 of the MSH2 gene, results from an A to T substitution at nucleotide position 901. This changes the amino acid from a lysine to a stop codon within coding exon 5. This mutation was seen in patient with colorectal cancer that showed high microsatellite instability (MSI-H) and loss of MSH2 protein staining on IHC, with a family history meeting Bethesda criteria (Mangold E et al. J Pathol, 2005 Dec;207:385-95; Mangold E et al. Int J Cancer, 2005 Sep;116:692-702). In addition to the clinical data presented in the literature, 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.
Revvity Omics, Revvity RCV003144124 SCV003831409 likely pathogenic not provided 2022-06-28 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003452974 SCV004188092 pathogenic Lynch syndrome 1 2023-07-28 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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