ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1857T>G (p.Tyr619Ter)

dbSNP: rs63750312
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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) RCV000076303 SCV000107324 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Invitae RCV000688460 SCV000816072 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-08-02 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 (PMID: 8613431, 11754112, 15849733, 19723918). ClinVar contains an entry for this variant (Variation ID: 90802). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr619*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002408598 SCV002721872 pathogenic Hereditary cancer-predisposing syndrome 2018-05-08 criteria provided, single submitter clinical testing The p.Y619* pathogenic mutation (also known as c.1857T>G), located in coding exon 12 of the MSH2 gene, results from a T to G substitution at nucleotide position 1857. This changes the amino acid from a tyrosine to a stop codon within coding exon 12. This alteration was first reported in a Japanese kindred that met Amsterdam criteria for Lynch syndrome (Lu SL et al. Jpn. J. Cancer Res., 1996 Mar;87:279-87; Bai YQ et al. Int. J. Cancer, 1999 Aug;82:512-5). This alteration was also reported by a German group in an individual diagnosed with MSI-H colon cancer at 45 that displayed absent MSH2 staining on immunohistochemistry (IHC) and family history met Amsterdam I criteria for Lynch syndrome (Krüger S et al. Hum. Mutat., 2002 Jan;19:82). 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. RCV003452862 SCV004186992 pathogenic Lynch syndrome 1 2023-08-03 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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