ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1408del (p.Leu469_Val470insTer)

dbSNP: rs63750384
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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) RCV000076153 SCV000107169 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000491004 SCV000580491 pathogenic Hereditary cancer-predisposing syndrome 2022-04-29 criteria provided, single submitter clinical testing The c.1408delG pathogenic mutation, located in coding exon 9 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1408, causing a translational frameshift with a predicted alternate stop codon (p.V470*). This alteration has been identified in cohorts of families suspected of Lynch syndrome (Scott RJ et al. Am J Hum Genet, 2001 Jan;68:118-127; Mangold E et al. Int J Cancer, 2005 Sep;116:692-702). This alteration has also been identified in individuals diagnosed with colorectal cancer and sebaceous adenomas (Mueller-Koch Y et al. Gut, 2005 Dec;54:1733-40; Everett JN et al. JAMA Dermatol, 2014 Dec;150:1315-21). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Invitae RCV000796731 SCV000936256 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-05-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been observed in several individuals affected with Lynch syndrome-associated cancers (PMID: 11112663, 15955785, 15849733, 25006859). ClinVar contains an entry for this variant (Variation ID: 90657). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val470*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV003452831 SCV004186805 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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