ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.566A>T (p.Lys189Met)

gnomAD frequency: 0.00001  dbSNP: rs1060502889
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575943 SCV000662393 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-03 criteria provided, single submitter clinical testing The p.K189M variant (also known as c.566A>T), located in coding exon 3 of the MSH6 gene, results from an A to T substitution at nucleotide position 566. The lysine at codon 189 is replaced by methionine, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000824111 SCV000964994 benign Hereditary nonpolyposis colorectal neoplasms 2022-11-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271528 SCV002555662 uncertain significance not specified 2022-06-06 criteria provided, single submitter clinical testing Variant summary: MSH6 c.566A>T (p.Lys189Met) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251438 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.566A>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Baylor Genetics RCV004569113 SCV005054959 uncertain significance Endometrial carcinoma 2024-01-22 criteria provided, single submitter clinical testing

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