Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013008 | SCV001173538 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | The p.S59P variant (also known as c.175T>C), located in coding exon 3 of the SDHD gene, results from a T to C substitution at nucleotide position 175. The serine at codon 59 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001860730 | SCV002113020 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 59 of the SDHD protein (p.Ser59Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. ClinVar contains an entry for this variant (Variation ID: 820002). 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 expected to disrupt SDHD protein function. 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. |
| Fulgent Genetics, |
RCV002489518 | SCV002801540 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Mitochondrial complex 2 deficiency, nuclear type 3 | 2022-04-23 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004569914 | SCV005056677 | uncertain significance | Mitochondrial complex 2 deficiency, nuclear type 3 | 2024-01-04 | criteria provided, single submitter | clinical testing |