Submissions for variant NM_000179.3(MSH6):c.908dup (p.Met303fs)

dbSNP: rs1057517551

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000411044	SCV000488242	likely pathogenic	Lynch syndrome 5	2016-02-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000473148	SCV000551210	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2024-11-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Met303Ilefs*9) 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: 371820). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000482391	SCV000572163	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	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; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30787465, 18269114, 24362816)
Ambry Genetics	RCV000491372	SCV000580314	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-23	criteria provided, single submitter	clinical testing	The c.908dupT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of T at nucleotide position 908, causing a translational frameshift with a predicted alternate stop codon (p.M303Ifs*9). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000482391	SCV001134461	pathogenic	not provided	2019-03-11	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Myriad Genetics, Inc.	RCV000411044	SCV004018860	pathogenic	Lynch syndrome 5	2023-03-27	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.