NM_000033.4(ABCD1):c.593C>T (p.Thr198Met) AND Adrenoleukodystrophy

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 27, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000761214.4

Allele description [Variation Report for NM_000033.4(ABCD1):c.593C>T (p.Thr198Met)]

NM_000033.4(ABCD1):c.593C>T (p.Thr198Met)

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.593C>T (p.Thr198Met)
HGVS:
  • NC_000023.11:g.153725859C>T
  • NG_009022.2:g.5992C>T
  • NG_023231.1:g.3888G>A
  • NM_000033.4:c.593C>TMANE SELECT
  • NP_000024.2:p.Thr198Met
  • LRG_1017t1:c.593C>T
  • LRG_1017:g.5992C>T
  • LRG_1017p1:p.Thr198Met
  • NC_000023.10:g.152991314C>T
  • NM_000033.3:c.593C>T
Protein change:
T198M
Links:
dbSNP: rs1569540704
NCBI 1000 Genomes Browser:
rs1569540704
Molecular consequence:
  • NM_000033.4:c.593C>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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000891167Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesotacriteria provided, single submitter
Likely pathogenic
(Aug 9, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001373941Invitaecriteria provided, single submitter
Pathogenic
(Aug 27, 2019)
germlineclinical testing

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

SCV001469223Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical Cityno assertion criteria providedPathogenic
(Jun 7, 2020)
germlineclinical testing

Summary from all submissions

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

X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism.

Wang Y, Busin R, Reeves C, Bezman L, Raymond G, Toomer CJ, Watkins PA, Snowden A, Moser A, Naidu S, Bibat G, Hewson S, Tam K, Clarke JT, Charnas L, Stetten G, Karczeski B, Cutting G, Steinberg S.

Mol Genet Metab. 2011 Sep-Oct;104(1-2):160-6. doi: 10.1016/j.ymgme.2011.05.016. Epub 2011 Jun 22.

PubMed [citation]
PMID:
21700483
See all PubMed Citations (5)

Details of each submission

From Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota, SCV000891167.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001373941.2

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

Description

This sequence change replaces threonine with methionine at codon 198 of the ABCD1 protein (p.Thr198Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with clinical and/or biochemical features of adrenoleukodystrophy (PMID: 21700483, 31074578, Invitae). ClinVar contains an entry for this variant (Variation ID: 623114). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Thr198 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in individuals with ABCD1-related conditions (PMID: 11748843), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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

From Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City, SCV001469223.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 27, 2021

Support Center