Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002536208 | SCV003294115 | likely pathogenic | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2022-06-09 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Tyr114 amino acid residue in SDHD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11343322, 16080474, 16317055, 17563904, 22456618, 23175444). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 694526). This missense change has been observed in individual(s) with paraganglioma (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 114 of the SDHD protein (p.Tyr114His). |
| All of Us Research Program, |
RCV004002908 | SCV004822209 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces tyrosine with histidine at codon 114 of the SDHD protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SDHD-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Institute of Human Genetics, |
RCV000856585 | SCV000999073 | uncertain significance | Pheochromocytoma | no assertion criteria provided | clinical testing |