Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002230194 | SCV000554048 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2023-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 73 of the SDHD protein (p.Ser73Gly). This variant is present in population databases (rs748545223, gnomAD 0.01%). 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: 412499). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800690 | SCV002047003 | uncertain significance | not specified | 2021-04-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002429558 | SCV002731468 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-08 | criteria provided, single submitter | clinical testing | The p.S73G variant (also known as c.217A>G), located in coding exon 3 of the SDHD gene, results from an A to G substitution at nucleotide position 217. The serine at codon 73 is replaced by glycine, an amino acid with similar properties. This variant was detected in 2/314 Chinese pheochromocytoma or paraganglioma (PPGL) patients (Ma X et al. Front Endocrinol (Lausanne), 2020 Dec;11:574662). This variant was also identified in 1/190 unrelated Chinese patients under the age of 45 who presented with renal tumors (Wu J et al. Cancer, 2019 04;125:1060-1069). 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. |