Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002453732 | SCV002617555 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-04-14 | criteria provided, single submitter | clinical testing | The p.S1201* pathogenic mutation (also known as c.3602C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 3602. This changes the amino acid from a serine to a stop codon within coding exon 15. This alteration occurs at the 3' terminus of theAPC gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 1643 amino acids of the protein. However, premature stop codons are typically deleterious in nature, the impacted region is critical for protein function, and a significant portion of the protein is affected (Ambry internal data). This mutation has been detected in an individual with a personal history of colon polyposis (Ambry internal data). Another alteration, c.3602C>G, that results in the same premature stop codon, p.S1201*, has been reported in multiple patients with familial adenomatous polyposis (FAP) (Aretz S et al. Eur J Hum Genet, 2004 Jan;12:52-8; Friedl W et al. Hered Cancer Clin Pract, 2005 Sep;3:95-114; Susswein LR et al. Genet Med, 2016 08;18:823-32). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Mayo Clinic Laboratories, |
RCV000202226 | SCV000256974 | likely pathogenic | not provided | no assertion criteria provided | research |