Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001910917 | SCV002162392 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 42 of the SDHD protein (p.Glu42Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs756995021, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. 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. |
| Ambry Genetics | RCV002397852 | SCV002672145 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.E42K variant (also known as c.124G>A), located in coding exon 2 of the SDHD gene, results from a G to A substitution at nucleotide position 124. The glutamic acid at codon 42 is replaced by lysine, 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. |