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NM_000061.3(BTK):c.1762T>C (p.Trp588Arg) AND X-linked agammaglobulinemia with growth hormone deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 12, 2022
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:
RCV003513680.2

Allele description [Variation Report for NM_000061.3(BTK):c.1762T>C (p.Trp588Arg)]

NM_000061.3(BTK):c.1762T>C (p.Trp588Arg)

Gene:
BTK:Bruton tyrosine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq22.1
Genomic location:
Preferred name:
NM_000061.3(BTK):c.1762T>C (p.Trp588Arg)
HGVS:
  • NC_000023.11:g.101353340A>G
  • NG_009616.1:g.37885T>C
  • NG_011734.1:g.630T>C
  • NM_000061.3:c.1762T>CMANE SELECT
  • NM_001287344.2:c.1864T>C
  • NM_001287345.2:c.1234T>C
  • NP_000052.1:p.Trp588Arg
  • NP_000052.1:p.Trp588Arg
  • NP_001274273.1:p.Trp622Arg
  • NP_001274274.1:p.Trp412Arg
  • LRG_128t1:c.1762T>C
  • LRG_128:g.37885T>C
  • LRG_128p1:p.Trp588Arg
  • NC_000023.10:g.100608328A>G
  • NM_000061.2:c.1762T>C
Protein change:
W412R
Molecular consequence:
  • NM_000061.3:c.1762T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287344.2:c.1864T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287345.2:c.1234T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
X-linked agammaglobulinemia with growth hormone deficiency (IGHD3)
Synonyms:
IGHD III; Isolated growth hormone deficiency type 3; Growth hormone deficiency with hypogammaglobulinemia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010615; MedGen: C0472813; Orphanet: 631; OMIM: 307200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004300154Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 12, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Characterization of novel Bruton's tyrosine kinase gene mutations in Central European patients with agammaglobulinemia.

Kristufek D, Aspalter RM, Eibl MM, Wolf HM.

Mol Immunol. 2007 Mar;44(7):1639-43. Epub 2006 Oct 12.

PubMed [citation]
PMID:
17045652

BTK: 22 novel and 25 recurrent mutations in European patients with X-linked agammaglobulinemia.

Fiorini M, Franceschini R, Soresina A, Schumacher RF, Ugazio AG, Rossi P, Plebani A, Notarangelo LD.

Hum Mutat. 2004 Mar;23(3):286.

PubMed [citation]
PMID:
14974089
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004300154.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 588 of the BTK protein (p.Trp588Arg). This missense change has been observed in individual(s) with agammaglobulinemia (PMID: 17045652). 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. This variant disrupts the p.Trp588 amino acid residue in BTK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14974089, 26931785). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 BTK protein function.

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

Last Updated: Sep 29, 2024