Submissions for variant NM_000179.3(MSH6):c.1777C>T (p.Gln593Ter)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002404010	SCV002714846	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-21	criteria provided, single submitter	clinical testing	The p.Q593* pathogenic mutation (also known as c.1777C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 1777. This changes the amino acid from a glutamine 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.
Myriad Genetics, Inc.	RCV003454284	SCV004185710	pathogenic	Lynch syndrome 5	2023-08-15	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV005055459	SCV005689661	likely pathogenic	Lynch syndrome	2025-02-04	criteria provided, single submitter	clinical testing	PVS1; PM2_SUP;
Labcorp Genetics (formerly Invitae), Labcorp	RCV005097750	SCV005843434	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2025-01-07	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln593*) 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: 1779901). For these reasons, this variant has been classified as Pathogenic.