Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002233436 | SCV000835523 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 39 of the SDHD protein (p.Pro39Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with pheochromocytoma and/or paraganglioma (PMID: 34906457). ClinVar contains an entry for this variant (Variation ID: 582411). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHD protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001010098 | SCV001170246 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-20 | criteria provided, single submitter | clinical testing | The p.P39L variant (also known as c.116C>T), located in coding exon 2 of the SDHD gene, results from a C to T substitution at nucleotide position 116. The proline at codon 39 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Genetic Services Laboratory, |
RCV001816738 | SCV002064682 | uncertain significance | not specified | 2019-07-16 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003472251 | SCV004203105 | uncertain significance | Mitochondrial complex 2 deficiency, nuclear type 3 | 2023-06-28 | criteria provided, single submitter | clinical testing |