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NM_001370658.1(BTD):c.1552C>T (p.Arg518Cys)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
11 (Most recent: Oct 4, 2021)
Last evaluated:
Sep 1, 2021
Accession:
VCV000001898.9
Variation ID:
1898
Description:
single nucleotide variant
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NM_001370658.1(BTD):c.1552C>T (p.Arg518Cys)

Allele ID
16937
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p25.1
Genomic location
3: 15645468 (GRCh38) GRCh38 UCSC
3: 15686975 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P43251:p.Arg538Cys
NC_000003.11:g.15686975C>T
NM_001281723.3:c.1552C>T NP_001268652.2:p.Arg518Cys missense
... more HGVS
Protein change
R518C
Other names
R538C
Canonical SPDI
NC_000003.12:15645467:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00014
Links
ClinGen: CA220320
Genetic Testing Registry (GTR): GTR000167612
UniProtKB: P43251#VAR_005121
OMIM: 609019.0003
dbSNP: rs80338686
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Sep 1, 2021 RCV000790794.3
Pathogenic 8 criteria provided, multiple submitters, no conflicts Dec 19, 2019 RCV000001975.13
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BTD - - GRCh38
GRCh37
427 464

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Apr 02, 2018)
criteria provided, single submitter
Method: clinical testing
Biotinidase deficiency
Allele origin: germline
Invitae
Accession: SCV000754947.2
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces arginine with cysteine at codon 538 of the BTD protein (p.Arg538Cys). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Biotinidase deficiency
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894302.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Oct 24, 2013)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000230006.5
Submitted: (Jun 30, 2017)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Sep 02, 2016)
criteria provided, single submitter
Method: clinical testing
Biotinidase deficiency
(Autosomal recessive inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000711423.1
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (1)
Comment:
The p.Arg538Cys variant in BTD has been previously identified in at least 5 comp ound heterozygous and 2 homozygous individuals with severe biotinidase deficienc y … (more)
Pathogenic
(Dec 19, 2019)
criteria provided, single submitter
Method: clinical testing
Biotinidase deficiency
Allele origin: unknown
Myriad Women's Health, Inc.
Accession: SCV001194032.2
Submitted: (Jun 18, 2020)
Evidence details
Publications
PubMed (2)
Comment:
NM_000060.2(BTD):c.1612C>T(R538C) is classified as pathogenic in the context of biotinidase deficiency. Sources cited for classification include the following: PMID 9099842 and 17185019. Classification of NM_000060.2(BTD):c.1612C>T(R538C) … (more)
Pathogenic
(Aug 10, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001470474.1
Submitted: (Dec 31, 2020)
Evidence details
Publications
PubMed (8)
Comment:
The best available variant frequency is uninformative because it is below the disease allele frequency. Found in at least one patient with expected phenotype for … (more)
Pathogenic
(Sep 01, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001962471.1
Submitted: (Oct 04, 2021)
Evidence details
pathologic
(Mar 15, 2011)
no assertion criteria provided
Method: curation
Biotinidase Deficiency
Allele origin: not provided
GeneReviews
Accession: SCV000040404.1
Submitted: (Jan 08, 2013)
Evidence details
Comment:
Converted during submission to Pathogenic.
Pathogenic
(Feb 17, 2017)
no assertion criteria provided
Method: literature only
Biotinidase deficiency
(Autosomal recessive inheritance)
Allele origin: germline
Research and Development, ARUP Laboratories
Accession: SCV000042698.2
Submitted: (Mar 10, 2017)
Evidence details
Publications
PubMed (1)
Pathogenic
(Apr 01, 1997)
no assertion criteria provided
Method: literature only
BIOTINIDASE DEFICIENCY
Allele origin: germline
OMIM
Accession: SCV000022133.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Biotinidase deficiency
Allele origin: germline
Natera, Inc.
Accession: SCV001461230.1
Submitted: (Dec 28, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Reconciling newborn screening and a novel splice variant in <i>BTD</i> associated with partial biotinidase deficiency: a BabySeq Project case report. Murry JB Cold Spring Harbor molecular case studies 2018 PMID: 29728376
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening. Wolf B Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 27657684
Biotinidase deficiency mimicking neuromyelitis optica beginning at the age of 4: A treatable disease. Girard B Multiple sclerosis (Houndmills, Basingstoke, England) 2017 PMID: 27207447
Biotinidase Deficiency Wolf B - 2016 PMID: 20301497
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 Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. Lazarin GA Genetics in medicine : official journal of the American College of Medical Genetics 2013 PMID: 22975760
Increased incidence of profound biotinidase deficiency among Hispanic newborns in California. Cowan TM Molecular genetics and metabolism 2012 PMID: 22698809
Mutations causing biotinidase deficiency in children ascertained by newborn screening in Western Hungary. Milánkovics I Molecular genetics and metabolism 2007 PMID: 17185019
Mutations in BTD causing biotinidase deficiency. Hymes J Human mutation 2001 PMID: 11668630
Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis. Pomponio RJ Pediatric research 1997 PMID: 9396567
Profound biotinidase deficiency caused by a point mutation that creates a downstream cryptic 3' splice acceptor site within an exon of the human biotinidase gene. Pomponio RJ Human molecular genetics 1997 PMID: 9158148
Arg538 to Cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children. Pomponio RJ Human genetics 1997 PMID: 9099842
Biotin-responsive alopecia and developmental regression. Charles BM Lancet (London, England) 1979 PMID: 88555
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD - - - -

Text-mined citations for rs80338686...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 08, 2021