Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001041775 | SCV001205412 | likely pathogenic | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-10-09 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 11 of the SDHA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the gain of 8 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is present in population databases (rs759806010, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 839910). Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in intron 11 (Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV003160278 | SCV003904157 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-11 | criteria provided, single submitter | clinical testing | The c.1551+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 11 of the SDHA gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame insertion of 8 amino acids; however, the exact functional impact of the inserted amino acids is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |