NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu) AND Adrenoleukodystrophy

Clinical significance:Pathogenic (Last evaluated: Aug 20, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000633485.3

Allele description [Variation Report for NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu)]

NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu)

Gene:
ABCD1:ATP binding cassette subfamily D member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu)
HGVS:
  • NC_000023.11:g.153740231C>T
  • NG_009022.2:g.20364C>T
  • NM_000033.4:c.1628C>TMANE SELECT
  • NP_000024.2:p.Pro543Leu
  • LRG_1017t1:c.1628C>T
  • LRG_1017:g.20364C>T
  • LRG_1017p1:p.Pro543Leu
  • NC_000023.10:g.153005685C>T
  • NM_000033.3:c.1628C>T
Protein change:
P543L
Links:
dbSNP: rs1557054776
NCBI 1000 Genomes Browser:
rs1557054776
Molecular consequence:
  • NM_000033.4:c.1628C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Adrenoleukodystrophy (ALD)
Synonyms:
ADDISON DISEASE AND CEREBRAL SCLEROSIS; BRONZE SCHILDER DISEASE; MELANODERMIC LEUKODYSTROPHY; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018544; MedGen: C0162309; OMIM: 300100

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000754718Invitaecriteria provided, single submitter
Pathogenic
(Aug 20, 2018)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.

Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, Cutting GR, Wanders RJ, Moser HW.

Hum Mutat. 2001 Dec;18(6):499-515. Review.

PubMed [citation]
PMID:
11748843

X-linked adrenoleukodystrophy in Spain. Identification of 26 novel mutations in the ABCD1 gene in 80 patients. Improvement of genetic counseling in 162 relative females.

Coll MJ, Palau N, Camps C, Ruiz M, Pàmpols T, Girós M.

Clin Genet. 2005 May;67(5):418-24.

PubMed [citation]
PMID:
15811009
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000754718.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces proline with leucine at codon 543 of the ABCD1 protein (p.Pro543Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with adrenoleukodystrophy (ALD) (PMID: 9242200, 10737980, 10980539, 11748843, 15811009, 24788897). This variant has also been reported in female carrierss affected with late-onset neurological symptoms (PMID: 24480483). Experimental studies have shown that this missense change results in absence of ALD protein (PMID: 11748843, 27067449). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 10, 2021

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