Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001919352 | SCV002189938 | uncertain significance | Orthostatic hypotension 1 | 2022-10-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with DBH-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 DBH protein function. ClinVar contains an entry for this variant (Variation ID: 1422074). This variant is present in population databases (rs151174779, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 359 of the DBH protein (p.Arg359Cys). |