ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.659A>G (p.Glu220Gly)

gnomAD frequency: 0.00001  dbSNP: rs764478569
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000206769 SCV000262353 benign Hereditary nonpolyposis colorectal neoplasms 2023-09-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000216982 SCV000276258 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-17 criteria provided, single submitter clinical testing The p.E220G variant (also known as c.659A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 659. The glutamic acid at codon 220 is replaced by glycine, an amino acid with 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000216982 SCV000690466 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-24 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 220 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 3/248928 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 RCV003997670 SCV004836764 uncertain significance Lynch syndrome 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 220 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 3/248928 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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