Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002234310 | SCV000937393 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2022-12-24 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SDHD-related conditions. 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: 643986). This variant is present in population databases (rs772671893, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 9 of the SDHD protein (p.Ala9Ser). |
| Ambry Genetics | RCV004027932 | SCV005020198 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-08 | criteria provided, single submitter | clinical testing | The p.A9S variant (also known as c.25G>T), located in coding exon 1 of the SDHD gene, results from a G to T substitution at nucleotide position 25. The alanine at codon 9 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |