ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.249G>C (p.Met83Ile)

dbSNP: rs1672552199
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001184668 SCV001350704 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-05 criteria provided, single submitter clinical testing This missense variant replaces methionine with isoleucine at codon 83 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. 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.
Ambry Genetics RCV001184668 SCV002742670 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-20 criteria provided, single submitter clinical testing The p.M83I variant (also known as c.249G>C), located in coding exon 2 of the MSH2 gene, results from a G to C substitution at nucleotide position 249. The methionine at codon 83 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003462656 SCV004196332 uncertain significance Lynch syndrome 1 2023-08-04 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004008477 SCV004832116 uncertain significance Lynch syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces methionine with isoleucine at codon 83 of the MSH2 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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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