ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2975A>G (p.Glu992Gly)

dbSNP: rs876660688
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219717 SCV000278320 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-27 criteria provided, single submitter clinical testing The p.E992G variant (also known as c.2975A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 2975. The glutamic acid at codon 992 is replaced by glycine, an amino acid with similar properties. This alteration has been reported as VUS in 1/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This amino acid position is not 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.
GeneKor MSA RCV000219717 SCV000822065 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000219717 SCV000904826 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-21 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 992 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 1/212948 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 RCV000792117 SCV000931395 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-07-13 criteria provided, single submitter clinical testing
Baylor Genetics RCV003463593 SCV004195538 uncertain significance Endometrial carcinoma 2023-09-02 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998583 SCV004839145 uncertain significance Lynch syndrome 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 992 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 1/212948 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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