ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.773T>C (p.Leu258Pro)
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(1); 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.773T>C (p.Leu258Pro)
Variation ID: 25045 Accession: VCV000025045.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15644689 (GRCh38) [ NCBI UCSC ] 3: 15686196 (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 Aug 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370658.1:c.773T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Leu258Pro missense NM_000060.4:c.833T>C NP_000051.1:p.Leu278Pro missense NM_001281723.4:c.773T>C NP_001268652.2:p.Leu258Pro missense NM_001281724.3:c.773T>C NP_001268653.2:p.Leu258Pro missense NM_001281725.3:c.773T>C NP_001268654.1:p.Leu258Pro missense NM_001323582.2:c.773T>C NP_001310511.1:p.Leu258Pro missense NM_001370752.1:c.773T>C NP_001357681.1:p.Leu258Pro missense NM_001370753.1:c.399+2632T>C intron variant NM_001407364.1:c.773T>C NP_001394293.1:p.Leu258Pro missense NM_001407365.1:c.773T>C NP_001394294.1:p.Leu258Pro missense NM_001407366.1:c.773T>C NP_001394295.1:p.Leu258Pro missense NM_001407367.1:c.773T>C NP_001394296.1:p.Leu258Pro missense NM_001407368.1:c.773T>C NP_001394297.1:p.Leu258Pro missense NM_001407369.1:c.773T>C NP_001394298.1:p.Leu258Pro missense NM_001407370.1:c.773T>C NP_001394299.1:p.Leu258Pro missense NM_001407371.1:c.773T>C NP_001394300.1:p.Leu258Pro missense NM_001407372.1:c.773T>C NP_001394301.1:p.Leu258Pro missense NM_001407373.1:c.773T>C NP_001394302.1:p.Leu258Pro missense NM_001407374.1:c.773T>C NP_001394303.1:p.Leu258Pro missense NM_001407375.1:c.773T>C NP_001394304.1:p.Leu258Pro missense NM_001407376.1:c.773T>C NP_001394305.1:p.Leu258Pro missense NM_001407377.1:c.773T>C NP_001394306.1:p.Leu258Pro missense NM_001407378.1:c.773T>C NP_001394307.1:p.Leu258Pro missense NM_001407379.1:c.773T>C NP_001394308.1:p.Leu258Pro missense NC_000003.12:g.15644689T>C NC_000003.11:g.15686196T>C NG_008019.2:g.48338T>C NG_008019.3:g.48339T>C - Protein change
- L258P
- Other names
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- Canonical SPDI
- NC_000003.12:15644688:T: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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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 |
667 | 753 |
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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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Aug 17, 2023 | RCV000021967.11 | |
Uncertain significance (1) |
no assertion criteria provided
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Jan 1, 2019 | RCV001251702.4 |
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
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
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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
(Sep 01, 2017)
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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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Counsyl
Accession: SCV000800585.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
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Likely pathogenic
(Mar 10, 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: SCV004211472.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Aug 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002301523.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant disrupts the p.Leu278 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: … (more)
This variant disrupts the p.Leu278 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 14707518), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BTD protein function. ClinVar contains an entry for this variant (Variation ID: 25045). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 9396567). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 278 of the BTD protein (p.Leu278Pro). (less)
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Uncertain significance
(Jan 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Intellectual disability
Affected status: yes
Allele origin:
unknown
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Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV001427443.1
First in ClinVar: Aug 15, 2020 Last updated: Aug 15, 2020 |
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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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Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies. | László A | Journal of inherited metabolic disease | 2003 | PMID: 14707518 |
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 |
Text-mined citations for rs397514389 ...
HelpRecord last updated Oct 08, 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.