Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000692290 | SCV000820104 | pathogenic | Hereditary pheochromocytoma-paraganglioma | 2023-07-06 | criteria provided, single submitter | clinical testing | Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 571215). Disruption of this splice site has been observed in individual(s) with bilateral pheochromocytoma (PMID: 20154675). This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change affects an acceptor splice site in intron 2 of the TMEM127 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV001015587 | SCV001176436 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-26 | criteria provided, single submitter | clinical testing | The c.245-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 2 of the TMEM127 gene. This alteration has been reported in individuals with personal history of pheochromocytoma (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. 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. |
New York Genome Center | RCV001420569 | SCV001622881 | likely pathogenic | Pheochromocytoma | 2020-06-19 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV001015587 | SCV002527244 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-08-17 | criteria provided, single submitter | curation |