ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.869T>C (p.Leu290Pro)

gnomAD frequency: 0.00001  dbSNP: rs751309721
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000473462 SCV000551124 benign Hereditary nonpolyposis colorectal neoplasms 2024-12-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000568053 SCV000662403 likely benign Hereditary cancer-predisposing syndrome 2018-06-27 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000568053 SCV000903795 likely benign Hereditary cancer-predisposing syndrome 2015-10-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985853 SCV001134459 uncertain significance not provided 2024-08-29 criteria provided, single submitter clinical testing The MSH6 c.869T>C (p.Leu290Pro) variant has been reported in an individual with endometrial cancer (PMID: 34115236 (2021)). The frequency of this variant in the general population, 0.000011 (3/282552 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Genetic Services Laboratory, University of Chicago RCV001821283 SCV002068661 uncertain significance not specified 2019-03-04 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000568053 SCV002536362 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-18 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV004001830 SCV004834834 likely benign Lynch syndrome 2023-05-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000985853 SCV005876959 uncertain significance not provided 2024-07-03 criteria provided, single submitter clinical testing The MSH6 c.869T>C; p.Leu290Pro variant (rs751309721, ClinVar Variation ID: 410443) is reported in the literature in and individual affected with endometrial cancer (Makabe 2021). This variant is found in the general population with an overall allele frequency of 0.001% (3/282,552 alleles) in the Genome Aggregation Database (v2.1.1). Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.194). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Makabe T et al. Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger. Int J Clin Oncol. 2021 Sep;26(9):1767-1774. PMID: 34115236.

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