Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000491912 | SCV000579872 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-07-27 | criteria provided, single submitter | clinical testing | The c.1312+2T>C intronic pathogenic mutation results from a T to C substitution two nucleotides after coding exon 9 in the APC gene. This nucleotide position is highly conserved in available vertebrate species. This mutation has been reported in a German family with FAP/AFAP (Friedl W and Aretz S. Hered Cancer Clin Pract 2005;3(3):95-114). Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |