ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2746A>C (p.Ile916Leu)

gnomAD frequency: 0.00001  dbSNP: rs751216225
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001016472 SCV001177431 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-22 criteria provided, single submitter clinical testing The p.I916L variant (also known as c.2746A>C), located in coding exon 16 of the MSH2 gene, results from an A to C substitution at nucleotide position 2746. The isoleucine at codon 916 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not 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.
Color Diagnostics, LLC DBA Color Health RCV001016472 SCV001347195 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with leucine at codon 916 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 3/248482 chromosomes 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.
Invitae RCV001860831 SCV002154805 benign Hereditary nonpolyposis colorectal neoplasms 2023-06-27 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004557 SCV004829964 uncertain significance Lynch syndrome 2023-06-28 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with leucine at codon 916 of the MSH2 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, 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 been identified in 3/248482 chromosomes 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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