ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.577del (p.His193fs)
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.577del (p.His193fs)
Variation ID: 590811 Accession: VCV000590811.6
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15644493 (GRCh38) [ NCBI UCSC ] 3: 15686000 (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 Nov 25, 2018 Feb 14, 2024 Dec 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370658.1:c.577del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.His193fs frameshift NM_000060.4:c.637delC NP_000051.1:p.His213Thrfs frameshift NM_001281723.4:c.577delC NP_001268652.2:p.His193Thrfs frameshift NM_001281724.3:c.577del NP_001268653.2:p.His193fs frameshift NM_001281725.3:c.577delC NP_001268654.1:p.His193Thrfs frameshift NM_001323582.2:c.577delC NP_001310511.1:p.His193Thrfs frameshift NM_001370752.1:c.577del NP_001357681.1:p.His193fs frameshift NM_001370753.1:c.399+2436del intron variant NM_001407364.1:c.577delC NP_001394293.1:p.His193Thrfs frameshift NM_001407365.1:c.577delC NP_001394294.1:p.His193Thrfs frameshift NM_001407366.1:c.577delC NP_001394295.1:p.His193Thrfs frameshift NM_001407367.1:c.577delC NP_001394296.1:p.His193Thrfs frameshift NM_001407368.1:c.577delC NP_001394297.1:p.His193Thrfs frameshift NM_001407369.1:c.577delC NP_001394298.1:p.His193Thrfs frameshift NM_001407370.1:c.577delC NP_001394299.1:p.His193Thrfs frameshift NM_001407371.1:c.577delC NP_001394300.1:p.His193Thrfs frameshift NM_001407372.1:c.577delC NP_001394301.1:p.His193Thrfs frameshift NM_001407373.1:c.577delC NP_001394302.1:p.His193Thrfs frameshift NM_001407374.1:c.577delC NP_001394303.1:p.His193Thrfs frameshift NM_001407375.1:c.577delC NP_001394304.1:p.His193Thrfs frameshift NM_001407376.1:c.577delC NP_001394305.1:p.His193Thrfs frameshift NM_001407377.1:c.577delC NP_001394306.1:p.His193Thrfs frameshift NM_001407378.1:c.577delC NP_001394307.1:p.His193Thrfs frameshift NM_001407379.1:c.577delC NP_001394308.1:p.His193Thrfs frameshift NC_000003.12:g.15644493del NC_000003.11:g.15686000del NG_008019.2:g.48142del NG_008019.3:g.48143del - Protein change
- H193fs
- Other names
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- Canonical SPDI
- NC_000003.12:15644492: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.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
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 |
643 | 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
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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 (2) |
criteria provided, single submitter
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Dec 17, 2023 | RCV000721974.5 |
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
(Dec 17, 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: SCV002233310.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.His213Thrfs*51) 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.His213Thrfs*51) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 331 amino acid(s) of the BTD protein. This variant is present in population databases (rs780874850, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with biotinidase deficiency (PMID: 29359854). ClinVar contains an entry for this variant (Variation ID: 590811). Studies have shown that this premature translational stop signal alters BTD gene expression (PMID: 29359854). 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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Likely pathogenic
(Jun 07, 2017)
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no assertion criteria provided
Method: curation
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Biotinidase deficiency
Affected status: no
Allele origin:
germline
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SingHealth Duke-NUS Institute of Precision Medicine
Accession: SCV000853124.1
First in ClinVar: Nov 25, 2018 Last updated: Nov 25, 2018 |
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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 |
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 |
Text-mined citations for rs780874850 ...
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.