Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004764385 | SCV005373708 | likely pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed frameshift variant c.335_336del(p.His112ArgfsTer9) in MLH1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.335_336del variant is absent in gnomAD Exomes. This variant causes a frameshift starting with codon Histidine 112, changes this amino acid to Arginine residue, and creates a premature Stop codon at position 9 of the new reading frame, denoted p.His112ArgfsTer9. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing (Thompson BA, et al., 2014). For these reasons, this variant has been classified as Likely Pathogenic. |