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NM_000061.3(BTK):c.1526T>C (p.Met509Thr) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 30, 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:
RCV003224377.8

Allele description [Variation Report for NM_000061.3(BTK):c.1526T>C (p.Met509Thr)]

NM_000061.3(BTK):c.1526T>C (p.Met509Thr)

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.1526T>C (p.Met509Thr)
HGVS:
  • NC_000023.11:g.101356092A>G
  • NG_009616.1:g.35133T>C
  • NM_000061.3:c.1526T>CMANE SELECT
  • NM_001287344.2:c.1628T>C
  • NM_001287345.2:c.1039-1398T>C
  • NP_000052.1:p.Met509Thr
  • NP_000052.1:p.Met509Thr
  • NP_001274273.1:p.Met543Thr
  • LRG_128t1:c.1526T>C
  • LRG_128:g.35133T>C
  • LRG_128p1:p.Met509Thr
  • NC_000023.10:g.100611080A>G
  • NM_000061.2:c.1526T>C
Protein change:
M509T
Links:
dbSNP: rs1569291644
NCBI 1000 Genomes Browser:
rs1569291644
Molecular consequence:
  • NM_001287345.2:c.1039-1398T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000061.3:c.1526T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287344.2:c.1628T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
X-linked agammaglobulinemia (XLA)
Synonyms:
IMMUNODEFICIENCY 1; Bruton's agammaglobulinemia; AGAMMAGLOBULINEMIA, X-LINKED, TYPE 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010421; MedGen: C0221026; Orphanet: 229717; Orphanet: 47; OMIM: 300755
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
SCV003920526Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Mar 30, 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920526.1

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

Description

BTK NM_000061.3 exon 15 p.Met509Thr (c.1526T>C): This variant has been reported in the literature in at least 4 individuals with X-Linked Agammaglobulinemia (XLA) (Noordzij 2002 PMID:12405164, Toth 2009 PMID:19419768, Lee 2010 PMID:19904586). This variant is not present in large control databases. This variant is present in ClinVar (Variation ID:571649). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Of note, other variants at this position have been reported in association with disease (p.Met509Ile, p.Met509Val) and at least 1 publication suggests that variants associated with disease are common at this position (Lee 1995 PMID:19904586). In summary, this variant is classified as pathogenic.

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

Last Updated: Nov 24, 2024