Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002231788 | SCV000640154 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2022-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 90 of the SDHD protein (p.Ala90Leu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. 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: 465230). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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. |
| Ambry Genetics | RCV000563970 | SCV000675127 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-05 | criteria provided, single submitter | clinical testing | The c.268_269delGCinsTT variant (also known as p.A90L), located in coding exon 3 of the SDHD gene, results from an in-frame deletion of GC and insertion of TT at nucleotide positions 268 to 269. This results in the substitution of the alanine residue for a leucine residue at codon 90, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003476276 | SCV004203110 | uncertain significance | Mitochondrial complex 2 deficiency, nuclear type 3 | 2023-05-06 | criteria provided, single submitter | clinical testing |