Total submissions: 2
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, |
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. |