Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002544819 | SCV000816227 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2022-07-11 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 568296). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 129 of the SDHD protein (p.Leu129Ser). |
| Ambry Genetics | RCV003163123 | SCV003906777 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-12 | criteria provided, single submitter | clinical testing | The p.L129S variant (also known as c.386T>C), located in coding exon 4 of the SDHD gene, results from a T to C substitution at nucleotide position 386. The leucine at codon 129 is replaced by serine, an amino acid with dissimilar 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. |
| Baylor Genetics | RCV003472194 | SCV004203087 | uncertain significance | Mitochondrial complex 2 deficiency, nuclear type 3 | 2023-10-17 | criteria provided, single submitter | clinical testing |