Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002396686 | SCV002699100 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-23 | criteria provided, single submitter | clinical testing | The c.1391-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 10 of the FH gene. 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. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with FH-related disease (Ambry internal data). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and may result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Another alteration impacting the same acceptor site (c.1391-2A>G) has been reported in a patient with FH-associated disease (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV003465720 | SCV004197351 | likely pathogenic | Fumarase deficiency | 2023-06-26 | criteria provided, single submitter | clinical testing |