ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3098T>A (p.Met1033Lys) (rs751035257)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000490990 SCV000580322 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-04 criteria provided, single submitter clinical testing The p.M1033K variant (also known as c.3098T>A), located in coding exon 4 of the MSH6 gene, results from a T to A substitution at nucleotide position 3098. The methionine at codon 1033 is replaced by lysine, an amino acid with few similar properties. This amino acid position is highly 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.
GeneDx RCV000521749 SCV000618327 uncertain significance not provided 2017-03-10 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3098T>A at the cDNA level, p.Met1033Lys (M1033K) at the protein level, and results in the change of a Methionine to a Lysine (ATG>AAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Met1033Lys was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Methionine and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH6 Met1033Lys occurs at a position that is conserved across species and is located within the Lever domain (Warren 2007, Kansikas 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether MSH6 Met1033Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659893 SCV000781790 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-11-01 criteria provided, single submitter clinical testing

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