ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3715A>G (p.Ile1239Val)

dbSNP: rs1469961964
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000629876 SCV000750832 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-06-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV002343196 SCV002619522 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-28 criteria provided, single submitter clinical testing The p.I1239V variant (also known as c.3715A>G), located in coding exon 8 of the MSH6 gene, results from an A to G substitution at nucleotide position 3715. The isoleucine at codon 1239 is replaced by valine, an amino acid with highly similar properties. This amino acid position is 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.
All of Us Research Program, National Institutes of Health RCV004002778 SCV004834842 uncertain significance Lynch syndrome 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1239 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 1/251224 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.
Baylor Genetics RCV004568359 SCV005055970 uncertain significance Endometrial carcinoma 2023-11-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005027741 SCV005658594 uncertain significance Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3 2024-05-15 criteria provided, single submitter clinical testing

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