ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.41_44del (p.Gly14fs)
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.
Pathogenic(2); Likely pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370658.1(BTD):c.41_44del (p.Gly14fs)
Variation ID: 631911 Accession: VCV000631911.46
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 3p25.1 3: 15635479-15635482 (GRCh38) [ NCBI UCSC ] 3: 15676986-15676989 (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 May 27, 2019 Mar 10, 2024 Oct 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370658.1:c.41_44del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Gly14fs frameshift NM_000060.4:c.101_104delGCTG NP_000051.1:p.Gly34Valfs frameshift NM_001281723.4:c.41_44delGCTG NP_001268652.2:p.Gly14Valfs frameshift NM_001281724.3:c.41_44del NP_001268653.2:p.Gly14fs frameshift NM_001281725.3:c.41_44delGCTG NP_001268654.1:p.Gly14Valfs frameshift NM_001281726.3:c.41_44delGCTG NP_001268655.2:p.Gly14Valfs frameshift NM_001323582.2:c.41_44delGCTG NP_001310511.1:p.Gly14Valfs frameshift NM_001370752.1:c.41_44del NP_001357681.1:p.Gly14fs frameshift NM_001370753.1:c.41_44del NP_001357682.1:p.Gly14fs frameshift NM_001407364.1:c.41_44delGCTG NP_001394293.1:p.Gly14Valfs frameshift NM_001407365.1:c.41_44delGCTG NP_001394294.1:p.Gly14Valfs frameshift NM_001407366.1:c.41_44delGCTG NP_001394295.1:p.Gly14Valfs frameshift NM_001407367.1:c.41_44delGCTG NP_001394296.1:p.Gly14Valfs frameshift NM_001407368.1:c.41_44delGCTG NP_001394297.1:p.Gly14Valfs frameshift NM_001407369.1:c.41_44delGCTG NP_001394298.1:p.Gly14Valfs frameshift NM_001407370.1:c.41_44delGCTG NP_001394299.1:p.Gly14Valfs frameshift NM_001407371.1:c.41_44delGCTG NP_001394300.1:p.Gly14Valfs frameshift NM_001407372.1:c.41_44delGCTG NP_001394301.1:p.Gly14Valfs frameshift NM_001407373.1:c.41_44delGCTG NP_001394302.1:p.Gly14Valfs frameshift NM_001407374.1:c.41_44delGCTG NP_001394303.1:p.Gly14Valfs frameshift NM_001407375.1:c.41_44delGCTG NP_001394304.1:p.Gly14Valfs frameshift NM_001407376.1:c.41_44delGCTG NP_001394305.1:p.Gly14Valfs frameshift NM_001407377.1:c.41_44delGCTG NP_001394306.1:p.Gly14Valfs frameshift NM_001407378.1:c.41_44delGCTG NP_001394307.1:p.Gly14Valfs frameshift NM_001407379.1:c.41_44delGCTG NP_001394308.1:p.Gly14Valfs frameshift NM_001407380.1:c.41_44delGCTG NP_001394309.1:p.Gly14Valfs frameshift NM_001407381.1:c.41_44delGCTG NP_001394310.1:p.Gly14Valfs frameshift NM_001407382.1:c.41_44delGCTG NP_001394311.1:p.Gly14Valfs frameshift NM_001407383.1:c.41_44delGCTG NP_001394312.1:p.Gly14Valfs frameshift NM_001407384.1:c.41_44delGCTG NP_001394313.1:p.Gly14Valfs frameshift NM_001407386.1:c.41_44delGCTG NP_001394315.1:p.Gly14Valfs frameshift NM_001407388.1:c.41_44delGCTG NP_001394317.1:p.Gly14Valfs frameshift NM_001407390.1:c.41_44delGCTG NP_001394319.1:p.Gly14Valfs frameshift NM_001407392.1:c.41_44delGCTG NP_001394321.1:p.Gly14Valfs frameshift NM_001407394.1:c.41_44delGCTG NP_001394323.1:p.Gly14Valfs frameshift NM_001407395.1:c.41_44delGCTG NP_001394324.1:p.Gly14Valfs frameshift NM_001407396.1:c.41_44delGCTG NP_001394325.1:p.Gly14Valfs frameshift NM_001407397.1:c.41_44delGCTG NP_001394326.1:p.Gly14Valfs frameshift NM_001407398.1:c.41_44delGCTG NP_001394327.1:p.Gly14Valfs frameshift NM_001407399.1:c.41_44delGCTG NP_001394328.1:p.Gly14Valfs frameshift NM_001407400.1:c.41_44delGCTG NP_001394329.1:p.Gly14Valfs frameshift NM_001407401.1:c.41_44delGCTG NP_001394330.1:p.Gly14Valfs frameshift NC_000003.12:g.15635480_15635483del NC_000003.11:g.15676987_15676990del NG_008019.2:g.39129_39132del - Protein change
- G14fs
- Other names
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- Canonical SPDI
- NC_000003.12:15635478:GGCTG:G
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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
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The frequency of the allele represented by this VCV record.
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- Links
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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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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 |
643 | 705 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Oct 24, 2023 | RCV000778682.13 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 1, 2018 | RCV001090471.16 |
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
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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
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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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Uncertain significance
(Oct 29, 2018)
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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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Illumina Laboratory Services, Illumina
Accession: SCV000915025.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The BTD c.101_104delGCTG (p.Gly34ValfsTer35) variant is a frameshift variant that is predicted to result in an absent or truncated protein. A literature search for the … (more)
The BTD c.101_104delGCTG (p.Gly34ValfsTer35) variant is a frameshift variant that is predicted to result in an absent or truncated protein. A literature search for the gene, cDNA change, and protein change did not reveal any clinical reports of this variant in individuals with biotinidase deficiency. In a retrospective analysis of carrier screening in 17638 chromosomes from ethnically diverse populations, Haque et al. (2016) identified the p.Gly34ValfsTer35 variant in one Caucasian allele. The variant is also reported at a frequency of 0.000363 in the European American population of the Exome Sequencing Project. Based on the potential impact of frameshift variants and the lack of clarifying evidence, the p.Gly34ValfsTer35 variant is classified as a variant of unknown significance but suspicious for pathogenicity for biotinidase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Likely pathogenic
(Feb 01, 2013)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: yes
Allele origin:
germline
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Arcensus
Accession: SCV002564587.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Oct 24, 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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Invitae
Accession: SCV001587423.4
First in ClinVar: May 10, 2021 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gly34Valfs*35) in the BTD gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gly34Valfs*35) in the BTD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BTD are known to be pathogenic (PMID: 20083419). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with biotinidase deficiency (PMID: 7550325, 27657684, 27845546, 28220409; Invitae). ClinVar contains an entry for this variant (Variation ID: 631911). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Dec 01, 2018)
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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: SCV001246038.19
First in ClinVar: May 12, 2020 Last updated: Mar 10, 2024 |
Number of individuals with the variant: 1
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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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Irreversibility of Symptoms with Biotin Therapy in an Adult with Profound Biotinidase Deficiency. | Ferreira P | JIMD reports | 2017 | PMID: 28220409 |
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 |
Clinical, Biochemical and Genetic Analysis of Biotinidase Deficiency in Iranian Population. | Asgari A | Archives of Iranian medicine | 2016 | PMID: 27845546 |
Modeled Fetal Risk of Genetic Diseases Identified by Expanded Carrier Screening. | Haque IS | JAMA | 2016 | PMID: 27533158 |
The identification of novel mutations in the biotinidase gene using denaturing high pressure liquid chromatography (dHPLC). | Iqbal F | Molecular genetics and metabolism | 2010 | PMID: 20083419 |
Mutational hotspot in the human biotinidase gene causes profound biotinidase deficiency. | Pomponio RJ | Nature genetics | 1995 | PMID: 7550325 |
Text-mined citations for rs1249246307 ...
HelpRecord last updated Mar 11, 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.