ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1442T>G (p.Leu481Ter)

dbSNP: rs786203036
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166169 SCV000216944 pathogenic Hereditary cancer-predisposing syndrome 2022-04-18 criteria provided, single submitter clinical testing The p.L481* pathogenic mutation (also known as c.1442T>G), located in coding exon 9 of the MSH2 gene, results from a T to G substitution at nucleotide position 1442. This changes the amino acid from a leucine to a stop codon within coding exon 9. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850337 SCV002143891 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-07-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) undergoing multigene panel testing for hereditary cancer (PMID: 28514183). A different variant (c.1442T>A) giving rise to the same protein effect has been determined to be pathogenic (Invitae). This suggests that this variant is also likely to be causative of disease. ClinVar contains an entry for this variant (Variation ID: 186554). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu481*) 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).

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