ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3160A>G (p.Ile1054Val)

dbSNP: rs267608075
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630191 SCV000751147 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-11-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV001018885 SCV001180179 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-10 criteria provided, single submitter clinical testing The p.I1054V variant (also known as c.3160A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 3160. The isoleucine at codon 1054 is replaced by valine, an amino acid with highly similar properties. This alteration was detected on a 25-gene panel test in a woman who was diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001018885 SCV001347206 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-24 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1054 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 been reported in an individual affected with breast cancer (PMID: 25186627). This variant has been identified in 1/246296 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 RCV004002795 SCV004837202 uncertain significance Lynch syndrome 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1054 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 hereditary cancer in the literature. This variant has been identified in 1/246296 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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