Submissions for variant NM_002439.5(MSH3):c.292A>T (p.Lys98Ter)

dbSNP: rs1749288232

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001234759	SCV001407418	pathogenic	not provided	2019-10-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys98*) in the MSH3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH3-related conditions. Loss-of-function variants in MSH3 are known to be pathogenic (PMID: 27476653). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002436919	SCV002752396	pathogenic	Hereditary cancer-predisposing syndrome	2021-07-14	criteria provided, single submitter	clinical testing	The p.K98* pathogenic mutation (also known as c.292A>T), located in coding exon 2 of the MSH3 gene, results from an A to T substitution at nucleotide position 292. This changes the amino acid from a lysine to a stop codon within coding exon 2. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Baylor Genetics	RCV003469429	SCV004197523	likely pathogenic	Endometrial carcinoma	2022-02-21	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004590257	SCV005082527	pathogenic	Familial adenomatous polyposis 4	2024-05-03	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.