Submissions for variant NM_000179.3(MSH6):c.3647-2_3991del

dbSNP: rs2104536268

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355019	SCV001549775	pathogenic	Endometrial carcinoma		no assertion criteria provided	clinical testing	The MSH6 c.3647-?_4083+?del variant (chr:2 g.48033343_48033999del GRCh37) results in a deletion of exons 8, 9 and 10, although the precise breakpoints of this deletion were not determined, nor were the effects of this variant on the resulting mRNA or protein product determined. The MSH6 p.Gly1216_Leu1360delinsAsp variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, UMD-LSDB, Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). This variant is a multi-exon in-frame deletion resulting in the removal of a glycine (gly) residue at codon 1216 and insertion of an aspartic acid (asp) residue at codon 1360 at the termination sequence; the impact of this alteration on MSH6 protein function is not known. This alteration is predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the MSH6 gene are an established mechanism of disease in Lynch syndrome and this is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.