Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000635252 | SCV000756638 | uncertain significance | Orthostatic hypotension 1 | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 164 of the DBH protein (p.Gly164Ser). This variant is present in population databases (rs142383279, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DBH-related conditions. ClinVar contains an entry for this variant (Variation ID: 529772). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Illumina Laboratory Services, |
RCV000635252 | SCV001329442 | uncertain significance | Orthostatic hypotension 1 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Baylor Genetics | RCV000635252 | SCV001530542 | uncertain significance | Orthostatic hypotension 1 | 2023-06-08 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004025458 | SCV004852691 | uncertain significance | Inborn genetic diseases | 2023-10-25 | criteria provided, single submitter | clinical testing | The c.490G>A (p.G164S) alteration is located in exon 3 (coding exon 3) of the DBH gene. This alteration results from a G to A substitution at nucleotide position 490, causing the glycine (G) at amino acid position 164 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |