Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001853704 | SCV002259620 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2021-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 16 of the SDHD protein (p.Gly16Cys). This variant is not present in population databases (gnomAD no frequency). 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: 465242). 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. |
| Revvity Omics, |
RCV003139772 | SCV003819253 | uncertain significance | not provided | 2019-05-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003139772 | SCV005080789 | uncertain significance | not provided | 2024-04-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV004659094 | SCV005161262 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-22 | criteria provided, single submitter | clinical testing | The p.G16C variant (also known as c.46G>T), located in coding exon 1 of the SDHD gene, results from a G to T substitution at nucleotide position 46. The glycine at codon 16 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003139772 | SCV005624059 | uncertain significance | not provided | 2024-10-25 | criteria provided, single submitter | clinical testing | The SDHD c.46G>T (p.Gly16Cys) variant has not been reported in individuals with SDHD-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |