Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001928163 | SCV002180127 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2021-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 19 of the SDHD protein (p.Leu19Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs574698019, ExAC 0.003%). This variant has not been reported in the literature in individuals with SDHD-related conditions. 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. 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 | RCV003167166 | SCV003906829 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-15 | criteria provided, single submitter | clinical testing | The p.L19P variant (also known as c.56T>C), located in coding exon 2 of the SDHD gene, results from a T to C substitution at nucleotide position 56. The leucine at codon 19 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. 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. |