Submissions for variant NM_000179.3(MSH6):c.2626G>T (p.Glu876Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002437249	SCV002745675	pathogenic	Hereditary cancer-predisposing syndrome	2018-01-11	criteria provided, single submitter	clinical testing	The p.E876* pathogenic mutation (also known as c.2626G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 2626. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003102044	SCV003230018	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2022-08-16	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu876*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816).
Baylor Genetics	RCV003465762	SCV004198141	likely pathogenic	Endometrial carcinoma	2022-07-09	criteria provided, single submitter	clinical testing