ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.905T>A (p.Leu302Ter)

dbSNP: rs63749914
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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) RCV000076747 SCV000107784 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Counsyl RCV000412047 SCV000488312 pathogenic Lynch syndrome 1 2016-02-25 criteria provided, single submitter clinical testing
Invitae RCV001224865 SCV001397091 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-10-23 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: 91242). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 14594944, 28449805, 28874130). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu302*) 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 RCV002444542 SCV002682890 pathogenic Hereditary cancer-predisposing syndrome 2023-08-16 criteria provided, single submitter clinical testing The p.L302* pathogenic mutation (also known as c.905T>A), located in coding exon 5 of the MSH2 gene, results from a T to A substitution at nucleotide position 905. This changes the amino acid from a leucine to a stop codon within coding exon 5. This alteration has been reported in Lynch syndrome patients whose personal and family cancer histories satisfy Amsterdam II criteria (Tomita N et al. Jpn. J. Clin. Oncol., 2003 Sep;33:486-9; Cruz-Correa M et al. Fam. Cancer, 2015 Sep;14:415-25). 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.
Myriad Genetics, Inc. RCV000412047 SCV004018345 pathogenic Lynch syndrome 1 2023-03-21 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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