Submissions for variant NM_000179.3(MSH6):c.4018A>G (p.Ser1340Gly)

dbSNP: rs1558395603

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	RCV000758617	SCV000887374	likely benign	Lynch syndrome	2018-05-01	criteria provided, single submitter	clinical testing	MSH6 NM_000179.2:c.4018A>G 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	RCV001021668	SCV001183314	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-02	criteria provided, single submitter	clinical testing	The p.S1340G variant (also known as c.4018A>G), located in coding exon 10 of the MSH6 gene, results from an A to G substitution at nucleotide position 4018. The serine at codon 1340 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. In addition, the CoDP in silico tool predicts this alteration to have minor impact on molecular function, with a score of 0.012 (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.