ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2307C>G (p.Tyr769Ter)

dbSNP: rs1573574086
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000820262 SCV000960968 pathogenic Hereditary nonpolyposis colorectal neoplasms 2024-03-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr769*) 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 variant has not been reported in the literature in individuals affected with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 662590). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002427049 SCV002731797 pathogenic Hereditary cancer-predisposing syndrome 2023-09-01 criteria provided, single submitter clinical testing The p.Y769* pathogenic mutation (also known as c.2307C>G), located in coding exon 14 of the MSH2 gene, results from a C to G substitution at nucleotide position 2307. This changes the amino acid from a tyrosine to a stop codon within coding exon 14. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. RCV003453724 SCV004186836 pathogenic Lynch syndrome 1 2023-08-08 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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