ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.733A>G (p.Ile245Val)

gnomAD frequency: 0.00006  dbSNP: rs762168786
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535308 SCV000624998 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571023 SCV000670034 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-15 criteria provided, single submitter clinical testing The p.I245V variant (also known as c.733A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 733. The isoleucine at codon 245 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000571023 SCV004357553 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-06 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 245 of the MSH6 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 MSH6-related disorders in the literature. This variant has been identified in 2/31410 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.
All of Us Research Program, National Institutes of Health RCV004003702 SCV004827913 uncertain significance Lynch syndrome 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 245 of the MSH6 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 MSH6-related disorders in the literature. This variant has been identified in 2/31410 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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