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NM_000787.4(DBH):c.1733A>C (p.Asn578Thr) AND Dopamine beta-hydroxylase deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 17, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001900947.1

Allele description

NM_000787.4(DBH):c.1733A>C (p.Asn578Thr)

Gene:
DBH:dopamine beta-hydroxylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.2
Genomic location:
Preferred name:
NM_000787.4(DBH):c.1733A>C (p.Asn578Thr)
HGVS:
  • NC_000009.12:g.133658326A>C
  • NG_008645.1:g.26964A>C
  • NM_000787.4:c.1733A>CMANE SELECT
  • NP_000778.3:p.Asn578Thr
  • NC_000009.11:g.136523448A>C
Protein change:
N578T
Molecular consequence:
  • NM_000787.4:c.1733A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dopamine beta-hydroxylase deficiency
Synonyms:
Norepinephrine deficiency; Noradrenaline deficiency; Dopamine beta-hydroxylase deficiency, congenital; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009123; MedGen: C4746777; Orphanet: 230; OMIM: 223360

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002158705Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 17, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV002158705.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces asparagine with threonine at codon 578 of the DBH protein (p.Asn578Thr). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with DBH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 23, 2022