Submissions for variant NM_000179.3(MSH6):c.260+2T>C

dbSNP: rs1553408469

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001991495	SCV002282083	likely pathogenic	Hereditary nonpolyposis colorectal neoplasms	2022-09-12	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This sequence change affects a donor splice site in intron 1 of the MSH6 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and is likely to result in the loss of the initiator methionine. This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 1495655). Studies have shown that disruption of this splice site results in skipping of exon 1, and is expected to result in the loss of the initiator methionine (Invitae). 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.
Myriad Genetics, Inc.	RCV003453944	SCV004189309	likely pathogenic	Lynch syndrome 5	2023-08-09	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.