ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.992del (p.Thr331fs)
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.992del (p.Thr331fs)
Variation ID: 25057 Accession: VCV000025057.13
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15644908 (GRCh38) [ NCBI UCSC ] 3: 15686415 (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 Apr 4, 2013 Feb 14, 2024 Oct 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370658.1:c.992del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Thr331fs frameshift NM_000060.2:c.1052delC NM_000060.4:c.1052del NM_000060.4:c.1052delC NP_000051.1:p.Thr351Lysfs frameshift NM_001281723.4:c.992delC NP_001268652.2:p.Thr331Lysfs frameshift NM_001281724.3:c.992del NP_001268653.2:p.Thr331fs frameshift NM_001281725.3:c.992delC NP_001268654.1:p.Thr331Lysfs frameshift NM_001323582.2:c.992delC NP_001310511.1:p.Thr331Lysfs frameshift NM_001370752.1:c.992del NP_001357681.1:p.Thr331fs frameshift NM_001370753.1:c.399+2851del intron variant NM_001407364.1:c.992delC NP_001394293.1:p.Thr331Lysfs frameshift NM_001407365.1:c.992delC NP_001394294.1:p.Thr331Lysfs frameshift NM_001407366.1:c.992delC NP_001394295.1:p.Thr331Lysfs frameshift NM_001407367.1:c.992delC NP_001394296.1:p.Thr331Lysfs frameshift NM_001407368.1:c.992delC NP_001394297.1:p.Thr331Lysfs frameshift NM_001407369.1:c.992delC NP_001394298.1:p.Thr331Lysfs frameshift NM_001407370.1:c.992delC NP_001394299.1:p.Thr331Lysfs frameshift NM_001407371.1:c.992delC NP_001394300.1:p.Thr331Lysfs frameshift NM_001407372.1:c.992delC NP_001394301.1:p.Thr331Lysfs frameshift NM_001407373.1:c.992delC NP_001394302.1:p.Thr331Lysfs frameshift NM_001407374.1:c.992delC NP_001394303.1:p.Thr331Lysfs frameshift NM_001407375.1:c.992delC NP_001394304.1:p.Thr331Lysfs frameshift NM_001407376.1:c.992delC NP_001394305.1:p.Thr331Lysfs frameshift NM_001407377.1:c.992delC NP_001394306.1:p.Thr331Lysfs frameshift NM_001407378.1:c.992delC NP_001394307.1:p.Thr331Lysfs frameshift NM_001407379.1:c.992delC NP_001394308.1:p.Thr331Lysfs frameshift NC_000003.12:g.15644908del NC_000003.11:g.15686415del NG_008019.2:g.48557del NG_008019.3:g.48558del - Protein change
- T331fs
- Other names
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- Canonical SPDI
- NC_000003.12:15644907:C:
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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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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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 |
645 | 705 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 28, 2023 | RCV000021980.10 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 13, 2020 | RCV000269677.4 |
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
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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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Pathogenic
(Nov 13, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600935.2
First in ClinVar: Dec 06, 2016 Last updated: Jan 03, 2022 |
Comment:
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in … (more)
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data. (less)
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Pathogenic
(May 23, 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: SCV004211459.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Sep 27, 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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GeneDx
Accession: SCV000329855.6
First in ClinVar: Dec 06, 2016 Last updated: Apr 17, 2019 |
Comment:
The c.1052delC variant in the BTD gene has been reported previously in association with biotinidase deficiency (Wolf et al. 2002; Iqbal et al. 2010; Gannavarapu … (more)
The c.1052delC variant in the BTD gene has been reported previously in association with biotinidase deficiency (Wolf et al. 2002; Iqbal et al. 2010; Gannavarapu et al. 2015). The c.1052delC variant has been reported to be associated with profound biotinidase deficiency in a patient who also harbored a second frameshift variant as well as in a patient homozygous for c.1052delC (Wolf et al. 2002; Iqbal et al. 2010). However, a second patient homozygous for c.1052delC was reported with partial biotinidase deficiency (Iqbal et al. 2010). The c.1052delC deletion causes a frameshift starting with codon Threonine 351, changes this amino acid to a Lysine residue and creates a premature Stop codon at position 12 of the new reading frame, denoted p.Thr351LysfsX12. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation. The c.1052delC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, we interpret c.1052delC to be a pathogenic variant. (less)
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Pathogenic
(Oct 28, 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: SCV001235508.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Thr351Lysfs*12) 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.Thr351Lysfs*12) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 193 amino acid(s) of the BTD protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with profound biotinidase deficiency (PMID: 12359137, 15776412, 20083419). ClinVar contains an entry for this variant (Variation ID: 25057). This variant disrupts a region of the BTD protein in which other variant(s) (p.Leu498Phefs*13) have been determined to be pathogenic (PMID: 17382128, 19728141, 29359854). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 09, 2016)
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no assertion criteria provided
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000486792.2
First in ClinVar: Apr 04, 2013 Last updated: Dec 23, 2019 |
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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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Clinical features, BTD gene mutations, and their functional studies of eight symptomatic patients with biotinidase deficiency from Southern China. | Liu Z | American journal of medical genetics. Part A | 2018 | PMID: 29359854 |
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 |
Diagnosis, treatment, follow-up and gene mutation analysis in four Chinese children with biotinidase deficiency. | Ye J | Journal of inherited metabolic disease | 2009 | PMID: 19728141 |
Hearing loss in biotinidase deficiency: genotype-phenotype correlation. | Sivri HS | The Journal of pediatrics | 2007 | PMID: 17382128 |
Biotinidase deficiency: novel mutations and their biochemical and clinical correlates. | Wolf B | Human mutation | 2005 | PMID: 15776412 |
Seventeen novel mutations that cause profound biotinidase deficiency. | Wolf B | Molecular genetics and metabolism | 2002 | PMID: 12359137 |
Text-mined citations for rs397514398 ...
HelpRecord last updated Feb 20, 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.