Submissions for variant NM_000179.3(MSH6):c.878_883delinsTTCG (p.Pro293fs)

dbSNP: rs1114167748

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000491677	SCV000580252	pathogenic	Hereditary cancer-predisposing syndrome	2020-08-26	criteria provided, single submitter	clinical testing	The c.878_883delCTGTCAinsTTCG pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from the deletion of 6 nucleotides and insertion of 4 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.P293Lfs*18). 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	RCV000695219	SCV000823704	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro293Leufs*18) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. For these reasons, this variant has been classified as Pathogenic.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center	RCV001523829	SCV001478128	pathogenic	Lynch syndrome 5	2020-12-15	criteria provided, single submitter	research
Myriad Genetics, Inc.	RCV001523829	SCV004185767	pathogenic	Lynch syndrome 5	2023-08-11	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics	RCV003470602	SCV004198113	likely pathogenic	Endometrial carcinoma	2022-11-17	criteria provided, single submitter	clinical testing
GeneDx	RCV004772937	SCV005384976	pathogenic	not provided	2024-04-24	criteria provided, single submitter	clinical testing	Observed in an individual with an embryonal rhabdomyosarcoma in the published literature (PMID: 34308366); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28873162, 34308366)