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NM_001370658.1(BTD):c.908A>G (p.His303Arg)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Pathogenic(1);Uncertain significance(5)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: Feb 21, 2021)
Last evaluated:
Jun 24, 2019
Accession:
VCV000038278.8
Variation ID:
38278
Description:
single nucleotide variant
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NM_001370658.1(BTD):c.908A>G (p.His303Arg)

Allele ID
46833
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p25.1
Genomic location
3: 15644824 (GRCh38) GRCh38 UCSC
3: 15686331 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P43251:p.His323Arg
NC_000003.12:g.15644824A>G
NG_008019.1:g.48077A>G
... more HGVS
Protein change
H303R
Other names
H323R
Canonical SPDI
NC_000003.12:15644823:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
0.00479 (G)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00013
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00205
Exome Aggregation Consortium (ExAC) 0.00232
1000 Genomes Project 0.00479
Links
ClinGen: CA220339
UniProtKB: P43251#VAR_005116
dbSNP: rs397507176
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Jan 27, 2019 RCV000723564.3
Likely pathogenic 1 criteria provided, single submitter Jul 7, 2017 RCV000622271.2
Conflicting interpretations of pathogenicity 5 criteria provided, conflicting interpretations Jun 24, 2019 RCV000021978.7
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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
Uncertain significance
(Dec 10, 2012)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000109921.8
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(Feb 15, 2018)
criteria provided, single submitter
Method: clinical testing
Biotinidase deficiency
Allele origin: germline
Invitae
Accession: SCV000630341.2
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces histidine with arginine at codon 323 of the BTD protein (p.His323Arg). The histidine residue is highly conserved and there is a … (more)
Uncertain significance
(Aug 02, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000516150.4
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The H323R variant in the BTD gene has been reported previously in the compound heterozygous state in a child with partial biotinidase deficiency at 22.5% … (more)
Uncertain significance
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Biotinidase deficiency
Allele origin: unknown
Mendelics
Accession: SCV001136346.1
Submitted: (Oct 22, 2019)
Evidence details
Uncertain significance
(Jan 27, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134045.2
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (6)
Likely pathogenic
(Jul 07, 2017)
criteria provided, single submitter
Method: clinical testing
Inborn genetic diseases
Allele origin: germline
Ambry Genetics
Accession: SCV000742653.2
Submitted: (Oct 09, 2020)
Evidence details
Publications
PubMed (5)
Pathogenic
(Jun 24, 2019)
criteria provided, single submitter
Method: clinical testing
Biotinidase deficiency
Allele origin: unknown
Baylor Genetics
Accession: SCV001522810.1
Submitted: (Feb 21, 2021)
Evidence details
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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: SCV000042648.2
Submitted: (Mar 10, 2017)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Sep 25, 2017)
no assertion criteria provided
Method: clinical testing
Biotinidase deficiency
Allele origin: germline
Natera, Inc.
Accession: SCV001454451.1
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
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
Analysis of protein-coding genetic variation in 60,706 humans. Lek M Nature 2016 PMID: 27535533
Neonatal screening for profound biotinidase deficiency in the Netherlands: consequences and considerations. Wiltink RC European journal of human genetics : EJHG 2016 PMID: 27329734
Biotinidase deficiency: Spectrum of molecular, enzymatic and clinical information from newborn screening Ontario, Canada (2007-2014). Gannavarapu S Molecular genetics and metabolism 2015 PMID: 26361991
Novel mutations causing biotinidase deficiency in individuals identified by newborn screening in Michigan including an unique intronic mutation that alters mRNA expression of the biotinidase gene. Li H Molecular genetics and metabolism 2014 PMID: 24797656
Biotinidase deficiency: an atypical presentation. Jagadeesh S The National medical journal of India 2013 PMID: 24066991
Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene. Swango KL Human genetics 1998 PMID: 9654207
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD - - - -

Text-mined citations for rs397507176...

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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