ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1345A>T (p.Lys449Ter)

dbSNP: rs63749920
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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) RCV000076128 SCV000107144 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Labcorp Genetics (formerly Invitae), Labcorp RCV001383406 SCV001582540 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-10-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys449*) 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 clinical features of MSH2-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 90632). 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.
Ambry Genetics RCV002381386 SCV002692375 pathogenic Hereditary cancer-predisposing syndrome 2019-04-23 criteria provided, single submitter clinical testing The p.K449* pathogenic mutation (also known as c.1345A>T), located in coding exon 8 of the MSH2 gene, results from an A to T substitution at nucleotide position 1345. This changes the amino acid from a lysine to a stop codon within coding exon 8. This variant has been reported in one Lynch syndrome family (Terdiman JP et al. Gastroenterology, 2001 Jan;120:21-30). 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.
Myriad Genetics, Inc. RCV003452823 SCV004187955 pathogenic Lynch syndrome 1 2023-08-01 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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