ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1120A>G (p.Lys374Glu)

dbSNP: rs1558660575
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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 RCV000692120 SCV000819928 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-08-30 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH6 protein function. ClinVar contains an entry for this variant (Variation ID: 571083). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 374 of the MSH6 protein (p.Lys374Glu).
Mendelics RCV000708863 SCV000837877 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002440455 SCV002748700 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-08 criteria provided, single submitter clinical testing The p.K374E variant (also known as c.1120A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 1120. The lysine at codon 374 is replaced by glutamic acid, an amino acid with similar properties. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Baylor Genetics RCV004569305 SCV005054838 uncertain significance Endometrial carcinoma 2024-03-19 criteria provided, single submitter clinical testing

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