Submissions for variant NM_000787.4(DBH):c.1772A>T (p.Glu591Val)

gnomAD frequency: 0.00096  dbSNP: rs75512464

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001065337	SCV001230293	uncertain significance	Orthostatic hypotension 1	2025-01-16	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 591 of the DBH protein (p.Glu591Val). This variant is present in population databases (rs75512464, 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: 859268). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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, Illumina	RCV001065337	SCV001329585	benign	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV003433009	SCV004156724	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	DBH: BP4