Submissions for variant NM_000249.4(MLH1):c.1367del (p.Thr455_Ser456insTer)

dbSNP: rs2125886267

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV003449998	SCV004189987	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-20	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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356088	SCV001551152	pathogenic	Carcinoma of colon		no assertion criteria provided	clinical testing	The MLH1 p.Ser456* variant was not identified in the literature nor was it identified in the dbSNP, ClinVar and UMD-LSDB databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.1367del variant leads to a premature stop codon at position 456 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the MLH1 gene are an established mechanism of disease in Lynch Syndrome and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.