ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.2148_2149del (p.Glu717fs)

dbSNP: rs1575639851
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001014572 SCV001175296 pathogenic Hereditary cancer-predisposing syndrome 2018-08-02 criteria provided, single submitter clinical testing The c.2148_2149delGG pathogenic mutation, located in coding exon 19 of the MLH1 gene, results from a deletion of two nucleotides at nucleotide positions 2148 to 2149, causing a translational frameshift with a predicted alternate stop codon (p.E717Tfs*5). Based on internal structural assessment, this alteration disrupts the structure of the C-terminal domain at the interface with PMS2 and the heterodimeric di-zinc endonuclease site (Gueneau E et al. Nat. Struct. Mol. Biol., 2013 Apr;20:461-8). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003455087 SCV004186293 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-25 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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