ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3965A>T (p.Glu1322Val)

gnomAD frequency: 0.00002  dbSNP: rs763608368
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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 RCV000491543 SCV000580326 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-04 criteria provided, single submitter clinical testing The p.E1322V variant (also known as c.3965A>T), located in coding exon 9 of the MSH6 gene, results from an A to T substitution at nucleotide position 3965. The glutamic acid at codon 1322 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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 RCV000491543 SCV001344760 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-16 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with valine at codon 1322 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 been identified in 4/248284 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 RCV001856944 SCV002199363 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-05-22 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004003464 SCV004835176 uncertain significance Lynch syndrome 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with valine at codon 1322 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 been identified in 4/248284 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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