ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1720C>T (p.Gln574Ter)

dbSNP: rs63751298
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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) RCV000076257 SCV000107277 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV002399460 SCV002714180 pathogenic Hereditary cancer-predisposing syndrome 2021-05-20 criteria provided, single submitter clinical testing The p.Q574* pathogenic mutation (also known as c.1720C>T), located in coding exon 11 of the MSH2 gene, results from a C to T substitution at nucleotide position 1720. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This alteration has been reported in multiple patients with features of Lynch syndrome (Mangold E et al. Int J Cancer, 2005 Sep;116:692-702; Nagasaka T et al. Cancer Res, 2010 Apr;70:3098-108). 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. RCV003452853 SCV004186868 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.
Color Diagnostics, LLC DBA Color Health RCV002399460 SCV004356698 pathogenic Hereditary cancer-predisposing syndrome 2021-12-20 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 11 of the MSH2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with Lynch syndrome or suspected Lynch syndrome (PMID: 15849733, 18550572, 27064304), or breast cancer (PMID: 27153395). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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