ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.16A>G (p.Lys6Glu)

dbSNP: rs777351049
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538201 SCV000625300 benign Hereditary nonpolyposis colorectal neoplasms 2023-11-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000562322 SCV000669849 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-27 criteria provided, single submitter clinical testing The p.K6E variant (also known as c.16A>G), located in coding exon 1 of the MSH2 gene, results from an A to G substitution at nucleotide position 16. The lysine at codon 6 is replaced by glutamic acid, an amino acid with similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759824 SCV000889423 uncertain significance not provided 2018-05-08 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000562322 SCV001356213 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-09 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 6 of the MSH2 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). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with breast cancer (PMID: 33471991), as well as healthy individuals (PMID: 29641532, 33471991). This variant has been identified in 1/221766 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.
Sema4, Sema4 RCV000562322 SCV002534398 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-09 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV004003738 SCV004826238 uncertain significance Lynch syndrome 2023-08-23 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 6 of the MSH2 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). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with breast cancer (PMID: 33471991), as well as healthy individuals (PMID: 29641532, 33471991). This variant has been identified in 1/221766 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.
Baylor Genetics RCV004568717 SCV005053481 uncertain significance Lynch syndrome 1 2024-01-22 criteria provided, single submitter clinical testing
GeneDx RCV000759824 SCV005325562 uncertain significance not provided 2023-11-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33471991, 18822302, 21120944, 29641532, 34326862)

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