Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075481 | SCV000106477 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV002415531 | SCV002724282 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-14 | criteria provided, single submitter | clinical testing | The c.2009delA pathogenic mutation, located in coding exon 18 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 2009, causing a translational frameshift with a predicted alternate stop codon (p.K670Rfs*113). This alteration occurs at the 3' terminus of MLH1 gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein by 25 amino acids. This frameshift impacts the last 88amino acids of the native protein. However, frameshifts are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |