Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003537460 | SCV001232145 | pathogenic | Familial adenomatous polyposis 1 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln203Asnfs*2) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 18433509, 20223039). ClinVar contains an entry for this variant (Variation ID: 860742). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002355088 | SCV002659891 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-11-11 | criteria provided, single submitter | clinical testing | The c.607delC pathogenic mutation, located in coding exon 5 of the APC gene, results from a deletion of one nucleotide at nucleotide position 607, causing a translational frameshift with a predicted alternate stop codon. This mutation (designated as p.Gln203fs) was identified in one Swedish patient with FAP diagnosed at age 40 who had duodenal adenomas in addition to 100-1000 colon polyps (Kanter-Smoler G et al. BMC Med 2008 Apr;6:10). This alteration was also reported in 2/1166 unrelated German index patients with a clinical diagnosis of FAP or AFAP (Friedl W et al. Hered Cancer Clin Pract 2005 Sep;3:95-114). A father and daughter with this mutation were found to have distal small bowel polyposis identified on capsule endoscopy (Schulmann K et al. Am. J. Gastroenterol. 2005 Jan;100:27-37). 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. |