Submissions for variant NM_000179.3(MSH6):c.3801+2T>G

dbSNP: rs1558392617

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002032981	SCV002112649	likely pathogenic	Hereditary nonpolyposis colorectal neoplasms	2024-08-21	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 8 of the MSH6 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 MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Lynch syndrome (PMID: 36073783). ClinVar contains an entry for this variant (Variation ID: 1347101). Studies have shown that disruption of this splice site is associated with inconclusive levels of altered splicing (internal data). 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.
University of Science and Technology Houari Boumediene, Laboratory of Molecular and Cellular Biology (LBCM)	RCV002284495	SCV002573629	likely pathogenic	Lynch syndrome 1		criteria provided, single submitter	clinical testing