ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1615T>C (p.Phe539Leu)

dbSNP: rs1558511106
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000773929 SCV000907629 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-19 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 539 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
MGZ Medical Genetics Center RCV002290018 SCV002580773 uncertain significance Lynch syndrome 1 2022-03-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004001338 SCV004833937 uncertain significance Lynch syndrome 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 539 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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