ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1238A>C (p.Gln413Pro)

gnomAD frequency: 0.00004  dbSNP: rs587779962
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212601 SCV000149408 uncertain significance not provided 2023-07-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18822302, 21120944)
Ambry Genetics RCV000115499 SCV000215745 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-03 criteria provided, single submitter clinical testing The p.Q413P variant (also known as c.1238A>C), located in coding exon 7 of the MSH2 gene, results from an A to C substitution at nucleotide position 1238. The glutamine at codon 413 is replaced by proline, an amino acid with similar properties. This variant was identified in a cohort of 3,579 African males diagnosed with prostate cancer who underwent multi-gene panel testing of 19 DNA repair and cancer predisposition genes (Matejcic M et al. JCO Precis Oncol, 2020 Jan;4:32-43). In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally neutral (Jia X et al. Am J Hum Genet, 2021 Jan;108:163-175). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000515341 SCV000611400 uncertain significance Lynch syndrome 1; Mismatch repair cancer syndrome 1; Muir-Torré syndrome 2017-05-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000532709 SCV000625241 benign Hereditary nonpolyposis colorectal neoplasms 2024-01-14 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000115499 SCV001359039 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-06 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000115499 SCV002528824 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-22 criteria provided, single submitter curation
Baylor Genetics RCV003467045 SCV004196186 uncertain significance Lynch syndrome 1 2023-10-16 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003997269 SCV004832657 uncertain significance Lynch syndrome 2023-06-27 criteria provided, single submitter clinical testing

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