Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076743 | SCV000107780 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV002444541 | SCV002682998 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-06-22 | criteria provided, single submitter | clinical testing | The c.888delC pathogenic mutation, located in coding exon 5 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 888, causing a translational frameshift with a predicted alternate stop codon (p.F296Lfs*5). This mutation has been reported in a family that met the Amsterdam criteria for HNPCC, and the mutation was present in three colorectal cancer cases as well as individuals with extracolonic cancers of the endometrium, ureter, and ovary. The youngest age at diagnosis of colorectal cancer was 32 years, and the median age was 61 years (Swensen J et al. Hum. Mutat., 1997;10:80-1). This mutation was identified in another family from a cohort of Danish individuals with suspected HNPCC, although specific clinical details were not provided (Nilbert M et al. Fam. Cancer, 2009 Jun;8:75-83). This mutation has been reported in an individual with a personal history of breast, colon and rectal cancers, as well as two unrelated patients with glioblastoma (Jensen UB et al. Breast Cancer Res. Treat., 2010 Apr;120:777-82; Therkildsen C et al. Eur. J. Neurol., 2015 Apr;22:717-24). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |