ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.677A>G (p.Glu226Gly)

dbSNP: rs587781777
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130018 SCV000184843 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-27 criteria provided, single submitter clinical testing The p.E226G variant (also known as c.677A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 677. The glutamic acid at codon 226 is replaced by glycine, an amino acid with similar properties. 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.
Counsyl RCV000410453 SCV000489006 uncertain significance Lynch syndrome 5 2016-08-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000130018 SCV000685515 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-06 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 226 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. In a large breast cancer case-control study, this variant was reported in 2/60466 cases and 0/53461 unaffected controls (PMID: 33471991). This variant has been identified in 1/250254 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000804545 SCV000944461 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-07-30 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000130018 SCV002536344 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-22 criteria provided, single submitter curation
Myriad Genetics, Inc. RCV000410453 SCV004019034 uncertain significance Lynch syndrome 5 2023-03-29 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health RCV003997541 SCV004836797 uncertain significance Lynch syndrome 2024-04-16 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 226 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. In a large breast cancer case-control study, this variant was reported in 2/60466 cases and 0/53461 unaffected controls (PMID: 33471991). This variant has been identified in 1/250254 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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