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NM_000033.4(ABCD1):c.1772G>C (p.Arg591Pro) AND Adrenoleukodystrophy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 17, 2023
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:
RCV003513723.2

Allele description [Variation Report for NM_000033.4(ABCD1):c.1772G>C (p.Arg591Pro)]

NM_000033.4(ABCD1):c.1772G>C (p.Arg591Pro)

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.1772G>C (p.Arg591Pro)
HGVS:
  • NC_000023.11:g.153740711G>C
  • NG_009022.2:g.20844G>C
  • NG_147800.1:g.331G>C
  • NM_000033.4:c.1772G>CMANE SELECT
  • NP_000024.2:p.Arg591Pro
  • LRG_1017t1:c.1772G>C
  • LRG_1017:g.20844G>C
  • LRG_1017p1:p.Arg591Pro
  • NC_000023.10:g.153006165G>C
Protein change:
R591P
Molecular consequence:
  • NM_000033.4:c.1772G>C - 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
SCV004298786Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Jan 17, 2023)
germlineclinical testing

PubMed (10)
[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

Altered expression of ALDP in X-linked adrenoleukodystrophy.

Watkins PA, Gould SJ, Smith MA, Braiterman LT, Wei HM, Kok F, Moser AB, Moser HW, Smith KD.

Am J Hum Genet. 1995 Aug;57(2):292-301.

PubMed [citation]
PMID:
7668254
PMCID:
PMC1801558

Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy.

Takano H, Koike R, Onodera O, Sasaki R, Tsuji S.

Arch Neurol. 1999 Mar;56(3):295-300.

PubMed [citation]
PMID:
10190819
See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298786.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg591 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7668254, 10190819, 12175782, 19129531, 22280810, 23566833, 24154795, 28503596). 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 ABCD1 protein function. This missense change has been observed in individual(s) with X-linked adrenoleukodystrophy (PMID: 23419472). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 591 of the ABCD1 protein (p.Arg591Pro).

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

Last Updated: Sep 29, 2024