Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001971617 | SCV002264032 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2022-07-05 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 1477485). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. This variant is present in population databases (rs749250498, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 137 of the SDHD protein (p.Ala137Val). |
| Ambry Genetics | RCV002324432 | SCV002632453 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-29 | criteria provided, single submitter | clinical testing | The p.A137V variant (also known as c.410C>T), located in coding exon 4 of the SDHD gene, results from a C to T substitution at nucleotide position 410. The alanine at codon 137 is replaced by valine, 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. |