ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2023G>A (p.Glu675Lys)

gnomAD frequency: 0.00001  dbSNP: rs878853713
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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 RCV000231201 SCV000283740 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-08-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000772336 SCV000905505 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-26 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 675 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 2/282258 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.
Ambry Genetics RCV000772336 SCV002724403 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-24 criteria provided, single submitter clinical testing The p.E675K variant (also known as c.2023G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 2023. The glutamic acid at codon 675 is replaced by lysine, an amino acid with similar properties. This amino acid position is 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.
Baylor Genetics RCV003463637 SCV004195655 uncertain significance Endometrial carcinoma 2023-07-16 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998714 SCV004838303 uncertain significance Lynch syndrome 2023-03-07 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 675 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 2/282258 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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