Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075708 | SCV000106712 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV003162486 | SCV003858870 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-07 | criteria provided, single submitter | clinical testing | The p.Q149* pathogenic mutation (also known as c.445C>T), located in coding exon 5 of the MLH1 gene, results from a C to T substitution at nucleotide position 445. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This alteration was identified in two individuals with a colorectal cancer diagnosis with microsatellite instability who met Amsterdam II criteria and was also detected in 1 of 537 French families tested for Lynch syndrome (de Jong AE et al. Clin Cancer Res, 2004 Feb;10:972-80; Bonadona V et al. JAMA, 2011 Jun;305:2304-10). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Myriad Genetics, |
RCV003451148 | SCV004189608 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-13 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |