Submissions for variant NM_000249.4(MLH1):c.2131dup (p.Ser711fs)

dbSNP: rs2148522538

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354285	SCV001548864	pathogenic	Carcinoma of colon		no assertion criteria provided	clinical testing	The MLH1 p.Ser711Phefs*12 variant was not identified in the literature nor was it identified in dbSNP, ClinVar, GeneInsight-COGR, Cosmic, UMD-LSDB, Zhejiang University Database, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors Database. 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.2131dup variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 711 and leads to a premature stop codon at position 722. This alteration is then predicted to result in 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. Of note, ClinVar lists multiple pathogenic premature stop codons that are located in the last exon of this gene. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.