Submissions for variant NM_000251.3(MSH2):c.201_211+3del

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV004442618	SCV004930971	likely pathogenic	Lynch syndrome 1	2024-03-11	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005104644	SCV005750136	likely pathogenic	Hereditary nonpolyposis colorectal neoplasms	2024-04-24	criteria provided, single submitter	clinical testing	This variant results in the deletion of part of exon 1 (c.201_211+3del) of the MSH2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 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 MSH2-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.