ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.830T>G (p.Leu277Ter)

dbSNP: rs786203424
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166723 SCV000217534 pathogenic Hereditary cancer-predisposing syndrome 2014-11-02 criteria provided, single submitter clinical testing The p.L277* pathogenic mutation (also known as c.830T>G), located in coding exon 5 of the MSH2 gene, results from a T to G substitution at nucleotide position 830. This changes the amino acid from a leucine to a stop codon within coding exon 5. This mutation was observed in a male diagnosed with MSI-H colon cancer at age 37, whose family met Bethesda criteria (Hampel, H et al. J Clin Oncol. 2008 Dec 10;26(35):5783-8). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Labcorp Genetics (formerly Invitae), Labcorp RCV001205245 SCV001376486 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-04-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu277*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 18809606, 28514183). ClinVar contains an entry for this variant (Variation ID: 187038). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003454416 SCV004186919 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.
Baylor Genetics RCV003454416 SCV004194532 pathogenic Lynch syndrome 1 2023-06-28 criteria provided, single submitter clinical testing

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