Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002233358 | SCV000830118 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2024-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 141 of the SDHD protein (p.Tyr141His). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 578342). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SDHD protein function with a positive predictive value of 95%. 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. |
| Fulgent Genetics, |
RCV000764955 | SCV000896128 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000986023 | SCV001134820 | uncertain significance | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | The SDHD c.421T>C (p.Tyr141His) variant has not been reported in individuals with SDHD-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/248750 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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 damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Ambry Genetics | RCV003165869 | SCV003906818 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-11 | criteria provided, single submitter | clinical testing | The p.Y141H variant (also known as c.421T>C), located in coding exon 4 of the SDHD gene, results from a T to C substitution at nucleotide position 421. The tyrosine at codon 141 is replaced by histidine, 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. |
| All of Us Research Program, |
RCV003999713 | SCV004825809 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-08-15 | criteria provided, single submitter | clinical testing |