ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.873del (p.Ser291fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370658.1(BTD):c.873del (p.Ser291fs)
Variation ID: 25052 Accession: VCV000025052.43
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15644789 (GRCh38) [ NCBI UCSC ] 3: 15686296 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 29, 2015 Apr 15, 2024 Oct 25, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370658.1:c.873del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Ser291fs frameshift NM_000060.2:c.933del NM_000060.2:c.933delT NM_000060.4:c.933del frameshift NM_000060.4:c.933delT NP_000051.1:p.Ser311Argfs frameshift NM_001281723.4:c.873delT NP_001268652.2:p.Ser291Argfs frameshift NM_001281724.3:c.873del NP_001268653.2:p.Ser291fs frameshift NM_001281725.3:c.873delT NP_001268654.1:p.Ser291Argfs frameshift NM_001323582.2:c.873delT NP_001310511.1:p.Ser291Argfs frameshift NM_001370752.1:c.873del NP_001357681.1:p.Ser291fs frameshift NM_001370753.1:c.399+2732del intron variant NM_001407364.1:c.873delT NP_001394293.1:p.Ser291Argfs frameshift NM_001407365.1:c.873delT NP_001394294.1:p.Ser291Argfs frameshift NM_001407366.1:c.873delT NP_001394295.1:p.Ser291Argfs frameshift NM_001407367.1:c.873delT NP_001394296.1:p.Ser291Argfs frameshift NM_001407368.1:c.873delT NP_001394297.1:p.Ser291Argfs frameshift NM_001407369.1:c.873delT NP_001394298.1:p.Ser291Argfs frameshift NM_001407370.1:c.873delT NP_001394299.1:p.Ser291Argfs frameshift NM_001407371.1:c.873delT NP_001394300.1:p.Ser291Argfs frameshift NM_001407372.1:c.873delT NP_001394301.1:p.Ser291Argfs frameshift NM_001407373.1:c.873delT NP_001394302.1:p.Ser291Argfs frameshift NM_001407374.1:c.873delT NP_001394303.1:p.Ser291Argfs frameshift NM_001407375.1:c.873delT NP_001394304.1:p.Ser291Argfs frameshift NM_001407376.1:c.873delT NP_001394305.1:p.Ser291Argfs frameshift NM_001407377.1:c.873delT NP_001394306.1:p.Ser291Argfs frameshift NM_001407378.1:c.873delT NP_001394307.1:p.Ser291Argfs frameshift NM_001407379.1:c.873delT NP_001394308.1:p.Ser291Argfs frameshift NC_000003.12:g.15644789del NC_000003.11:g.15686296del NG_008019.2:g.48438del NG_008019.3:g.48439del - Protein change
- S291fs
- Other names
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- Canonical SPDI
- NC_000003.12:15644788:T:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BTD | - | - |
GRCh38 GRCh37 |
645 | 705 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Oct 25, 2023 | RCV000021974.26 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 31, 2022 | RCV000078082.31 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jun 20, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000230007.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 4
Sex: mixed
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Pathogenic
(May 27, 2020)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001473123.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The BTD c.933delT; p.Ser311fs variant (rs397514395) is reported in the literature in the compound heterozygous state in multiple individuals affected with profound or partial biotinidase … (more)
The BTD c.933delT; p.Ser311fs variant (rs397514395) is reported in the literature in the compound heterozygous state in multiple individuals affected with profound or partial biotinidase deficiency (Borsatto 2014, Milankovics 2007, Pomponio 1997, Wolf 2002, Wolf 2017). This variant is found on only three chromosomes in the Genome Aggregation Database (3/282788 alleles), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide in the last exon of the BTD gene. While this is not expected to lead to nonsense-mediated decay, this is predicted to result in a truncated protein lacking the last 233 amino acids of the BTD protein. Based on available information, this variant is considered to be pathogenic. References: Borsatto T et al. Biotinidase deficiency: clinical and genetic studies of 38 Brazilian patients. BMC Med Genet. 2014;15:96. Milankovics I et al. Mutations causing biotinidase deficiency in children ascertained by newborn screening in Western Hungary. Mol Genet Metab. 2007;90(3):345-348. Pomponio RJ et al. Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis. Pediatr Res. 1997;42(6):840-848. Wolf B et al. Seventeen novel mutations that cause profound biotinidase deficiency. Mol Genet Metab. 2002;77(1-2):108-111. Wolf B. Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening. Genet Med. 2017;19(4):396-402. (less)
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Likely pathogenic
(Nov 24, 2021)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002814810.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Sep 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000630340.5
First in ClinVar: Dec 26, 2017 Last updated: Feb 07, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser311Argfs*23) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Ser311Argfs*23) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 233 amino acid(s) of the BTD protein. This variant is present in population databases (rs397514395, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with biotinidase deficiency (PMID: 9396567, 10400129, 12359137, 17185019, 22698809, 25174816, 27657684). ClinVar contains an entry for this variant (Variation ID: 25052). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000238755.14
First in ClinVar: Jul 18, 2015 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation, as the last 233 amino acids are replaced with 22 different amino acids, and other loss-of-function variants … (more)
Frameshift variant predicted to result in protein truncation, as the last 233 amino acids are replaced with 22 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20549359, 9396567, 10400129, 27657684) (less)
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Pathogenic
(Oct 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211396.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV004238793.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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Pathogenic
(Mar 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001500291.17
First in ClinVar: Mar 14, 2021 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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Likely pathogenic
(Jun 09, 2014)
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criteria provided, single submitter
Method: literature only
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Biotinidase deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220396.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Apr 06, 2020)
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no assertion criteria provided
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002081566.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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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: clinical and genetic studies of 38 Brazilian patients. | Borsatto T | BMC medical genetics | 2014 | PMID: 25174816 |
Increased incidence of profound biotinidase deficiency among Hispanic newborns in California. | Cowan TM | Molecular genetics and metabolism | 2012 | PMID: 22698809 |
High frequencies of biotinidase (BTD) gene mutations in the Hungarian population. | Milánkovics I | Journal of inherited metabolic disease | 2010 | PMID: 20549359 |
Mutations causing biotinidase deficiency in children ascertained by newborn screening in Western Hungary. | Milánkovics I | Molecular genetics and metabolism | 2007 | PMID: 17185019 |
Seventeen novel mutations that cause profound biotinidase deficiency. | Wolf B | Molecular genetics and metabolism | 2002 | PMID: 12359137 |
Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children. | Norrgard KJ | Pediatric research | 1999 | PMID: 10400129 |
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 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD | - | - | - | - |
Text-mined citations for rs397514395 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.