Submissions for variant NM_000179.3(MSH6):c.3185G>A (p.Cys1062Tyr)

dbSNP: rs1558386797

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
University of Washington Department of Laboratory Medicine, University of Washington	RCV000758678	SCV000887449	likely pathogenic	Lynch syndrome	2018-05-01	criteria provided, single submitter	clinical testing	MSH6 NM_000179.2:c.3185G>A has a 96.3% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 26.5 to 1, generated from evidence of seeing this as a somatic mutation in a tumor with loss of heterozygosity at the MSH6 locus. See Shirts et al 2018, PMID 29887214.
Ambry Genetics	RCV002325458	SCV002609228	uncertain significance	Hereditary cancer-predisposing syndrome	2022-04-07	criteria provided, single submitter	clinical testing	The p.C1062Y variant (also known as c.3185G>A), located in coding exon 5 of the MSH6 gene, results from a G to A substitution at nucleotide position 3185. The cysteine at codon 1062 is replaced by tyrosine, an amino acid with highly dissimilar properties. Using a Bayesian analysis that incorporates tumor mutation data, this variant was classified as likely pathogenic (Shirts BH et al. Am J Hum Genet, 2018 07;103:19-29). 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.