Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010913 | SCV001171174 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-12-30 | criteria provided, single submitter | clinical testing | The c.1312+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 9 of the APC gene. This nucleotide position is highly conserved in available vertebrate species. 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. While this exact alteration has not been reported in the literature, a mutation at the same position (c.1312+1G>A) has been reported in multiple individuals with familial adenomatous polyposis (Gavert N et al, Hum. Mutat. 2002 Jun; 19(6):664; Kerr SE, J Mol Diagn 2013 Jan; 15(1):31-43) with mRNA studies showing the c.1312+1G>A mutation causes aberrant splicing leading to a premature stop codon (Zhang S, Gene 2016 Feb; 577(2):187-92). 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. Based on the majority of available evidence to date, this alteration is classified as likely pathogenic. |