Submissions for variant NM_000179.3(MSH6):c.1281C>A (p.Tyr427Ter)

dbSNP: rs1553412720

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001217699	SCV001389548	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2024-05-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr427*) 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: 946768). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002379819	SCV002695299	pathogenic	Hereditary cancer-predisposing syndrome	2022-08-08	criteria provided, single submitter	clinical testing	The p.Y427* pathogenic mutation (also known as c.1281C>A), located in coding exon 4 of the MSH6 gene, results from a C to A substitution at nucleotide position 1281. This changes the amino acid from a tyrosine 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.	RCV003449686	SCV004188277	pathogenic	Lynch syndrome 5	2023-08-11	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.
Baylor Genetics	RCV004570494	SCV005055022	likely pathogenic	Endometrial carcinoma	2023-11-28	criteria provided, single submitter	clinical testing