Submissions for variant NM_000249.4(MLH1):c.963_1014dup (p.Ser339fs)

gnomAD frequency: 0.00001  dbSNP: rs1553648058

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500035	SCV000592390	pathogenic	Lynch syndrome	2016-03-23	criteria provided, single submitter	clinical testing
Invitae	RCV001242154	SCV001415223	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2019-10-07	criteria provided, single submitter	clinical testing	Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 433861). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser339Hisfs*40) in the MLH1 gene. It is expected to result in an absent or disrupted protein product.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV001258083	SCV001434925	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2018-10-15	criteria provided, single submitter	clinical testing	The c.963_1014dup (p.Ser339Hisfs*40) variant in the MLH1 gene is predicted to introduce a premature translation termination codon. This variant has never been reported in general population databases. Therefore, this c.963_1014dup (p.Ser339Hisfs*40) variant is classified as pathogenic.
Myriad Genetics, Inc.	RCV001258083	SCV004186571	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-19	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.