Submissions for variant NM_000179.3(MSH6):c.133G>T (p.Gly45Cys)

dbSNP: rs978968846

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	RCV000758663	SCV000887434	likely benign	Lynch syndrome	2018-05-01	criteria provided, single submitter	clinical testing	MSH6 NM_000179.2:c.133G>T has a 2.2% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 0.20 to 1, generated from evidence of seeing this as a somatic mutation in a tumor without loss of heterozygosity at the MSH6 locus. See Shirts et al 2018, PMID 29887214.
Ambry Genetics	RCV002386319	SCV002693640	uncertain significance	Hereditary cancer-predisposing syndrome	2018-08-25	criteria provided, single submitter	clinical testing	The p.G45C variant (also known as c.133G>T), located in coding exon 1 of the MSH6 gene, results from a G to T substitution at nucleotide position 133. The glycine at codon 45 is replaced by cysteine, an amino acid with highly dissimilar 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. In addition, the CoDP in silico tool predicts this alteration to have a minor impact on molecular function, with a score of 0.000 (Terui H et al. J. Biomed. Sci. 2013 Apr;20:25). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.