Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001359774 | SCV001555659 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 3 of the SDHB protein (p.Ala3Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 1051700). 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 SDHB 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. |
| Ambry Genetics | RCV003169783 | SCV003912994 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | The p.A3T variant (also known as c.7G>A), located in coding exon 1 of the SDHB gene, results from a G to A substitution at nucleotide position 7. The alanine at codon 3 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003473881 | SCV004202991 | uncertain significance | Gastrointestinal stromal tumor | 2023-08-31 | criteria provided, single submitter | clinical testing |