Submissions for variant NM_000179.3(MSH6):c.2079del (p.Lys693fs)

dbSNP: rs267608083

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000687847	SCV000815436	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2024-03-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys693Asnfs*43) 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. ClinVar contains an entry for this variant (Variation ID: 567689). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002422478	SCV002729834	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-29	criteria provided, single submitter	clinical testing	The c.2079delA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 2079, causing a translational frameshift with a predicted alternate stop codon (p.K693Nfs*43). 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.
Myriad Genetics, Inc.	RCV003453421	SCV004188292	pathogenic	Lynch syndrome 5	2023-08-16	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Molecular Genetics Lab, CHRU Brest	RCV003883159	SCV004697604	pathogenic	Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3		criteria provided, single submitter	clinical testing
Constitutional Genetics Lab, Leon Berard Cancer Center	RCV001249958	SCV001423972	pathogenic	Lynch-like syndrome	2019-07-01	no assertion criteria provided	clinical testing
Genomic Center, National Cancer Institute	RCV001293834	SCV001481765	pathogenic	Colorectal cancer		no assertion criteria provided	case-control