Submissions for variant NM_000251.3(MSH2):c.1487del (p.Thr495_Leu496insTer)

dbSNP: rs1573548065

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001384383	SCV001583842	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2021-03-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This nonsense change has been observed in individual(s) with Lynch syndrome (PMID: 17123147). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu496*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).
Ambry Genetics	RCV002395869	SCV002701639	pathogenic	Hereditary cancer-predisposing syndrome	2021-11-19	criteria provided, single submitter	clinical testing	The c.1487delT pathogenic mutation, located in coding exon 9 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1487, causing a translational frameshift with a predicted alternate stop codon (p.L496*). 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.
Myriad Genetics, Inc.	RCV003450062	SCV004188183	pathogenic	Lynch syndrome 1	2023-08-02	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.