This variant is present in population databases (rs780281959, gnomAD 0.006%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Val62 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11313766, 15060693, 17185019, 22698809). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with BTD-related conditions. This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 62 of the BTD protein (p.Val62Ala).
ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.125T>C (p.Val42Ala)
Germline
Classification
Help
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.
(1)
Help
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.
Likely pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370658.1(BTD):c.125T>C (p.Val42Ala)
Variation ID: 2918707 Accession: VCV002918707.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15635564 (GRCh38) [ NCBI UCSC ] 3: 15677071 (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 Feb 20, 2024 Feb 20, 2024 Nov 29, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370658.1:c.125T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Val42Ala missense NM_000060.4:c.185T>C NP_000051.1:p.Val62Ala missense NM_001281723.4:c.125T>C NP_001268652.2:p.Val42Ala missense NM_001281724.3:c.125T>C NP_001268653.2:p.Val42Ala missense NM_001281725.3:c.125T>C NP_001268654.1:p.Val42Ala missense NM_001281726.3:c.125T>C NP_001268655.2:p.Val42Ala missense NM_001323582.2:c.125T>C NP_001310511.1:p.Val42Ala missense NM_001370752.1:c.125T>C NP_001357681.1:p.Val42Ala missense NM_001370753.1:c.125T>C NP_001357682.1:p.Val42Ala missense NM_001407364.1:c.125T>C NP_001394293.1:p.Val42Ala missense NM_001407365.1:c.125T>C NP_001394294.1:p.Val42Ala missense NM_001407366.1:c.125T>C NP_001394295.1:p.Val42Ala missense NM_001407367.1:c.125T>C NP_001394296.1:p.Val42Ala missense NM_001407368.1:c.125T>C NP_001394297.1:p.Val42Ala missense NM_001407369.1:c.125T>C NP_001394298.1:p.Val42Ala missense NM_001407370.1:c.125T>C NP_001394299.1:p.Val42Ala missense NM_001407371.1:c.125T>C NP_001394300.1:p.Val42Ala missense NM_001407372.1:c.125T>C NP_001394301.1:p.Val42Ala missense NM_001407373.1:c.125T>C NP_001394302.1:p.Val42Ala missense NM_001407374.1:c.125T>C NP_001394303.1:p.Val42Ala missense NM_001407375.1:c.125T>C NP_001394304.1:p.Val42Ala missense NM_001407376.1:c.125T>C NP_001394305.1:p.Val42Ala missense NM_001407377.1:c.125T>C NP_001394306.1:p.Val42Ala missense NM_001407378.1:c.125T>C NP_001394307.1:p.Val42Ala missense NM_001407379.1:c.125T>C NP_001394308.1:p.Val42Ala missense NM_001407380.1:c.125T>C NP_001394309.1:p.Val42Ala missense NM_001407381.1:c.125T>C NP_001394310.1:p.Val42Ala missense NM_001407382.1:c.125T>C NP_001394311.1:p.Val42Ala missense NM_001407383.1:c.125T>C NP_001394312.1:p.Val42Ala missense NM_001407384.1:c.125T>C NP_001394313.1:p.Val42Ala missense NM_001407386.1:c.125T>C NP_001394315.1:p.Val42Ala missense NM_001407388.1:c.125T>C NP_001394317.1:p.Val42Ala missense NM_001407390.1:c.125T>C NP_001394319.1:p.Val42Ala missense NM_001407392.1:c.125T>C NP_001394321.1:p.Val42Ala missense NM_001407394.1:c.125T>C NP_001394323.1:p.Val42Ala missense NM_001407395.1:c.125T>C NP_001394324.1:p.Val42Ala missense NM_001407396.1:c.125T>C NP_001394325.1:p.Val42Ala missense NM_001407397.1:c.125T>C NP_001394326.1:p.Val42Ala missense NM_001407398.1:c.125T>C NP_001394327.1:p.Val42Ala missense NM_001407399.1:c.125T>C NP_001394328.1:p.Val42Ala missense NM_001407400.1:c.125T>C NP_001394329.1:p.Val42Ala missense NM_001407401.1:c.125T>C NP_001394330.1:p.Val42Ala missense NC_000003.12:g.15635564T>C NC_000003.11:g.15677071T>C NG_008019.2:g.39213T>C NG_008019.3:g.39214T>C - Protein change
- V62A, V42A
- Other names
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- Canonical SPDI
- NC_000003.12:15635563: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.
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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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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
Help
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. |
|||
| BTD | - | - |
GRCh38 GRCh37 |
667 | 753 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
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Nov 29, 2022 | RCV003601990.2 |
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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|---|---|---|---|---|---|
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Likely pathogenic
(Nov 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004554318.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This variant is present in population databases (rs780281959, gnomAD 0.006%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data … (more)
This variant is present in population databases (rs780281959, gnomAD 0.006%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Val62 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11313766, 15060693, 17185019, 22698809). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with BTD-related conditions. This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 62 of the BTD protein (p.Val62Ala). (less)
|
Comment:
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. |
Comment:
This variant is present in population databases (rs780281959, gnomAD 0.006%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Val62 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11313766, 15060693, 17185019, 22698809). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with BTD-related conditions. This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 62 of the BTD protein (p.Val62Ala).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Increased incidence of profound biotinidase deficiency among Hispanic newborns in California. | Cowan TM | Molecular genetics and metabolism | 2012 | PMID: 22698809 |
| Mutations causing biotinidase deficiency in children ascertained by newborn screening in Western Hungary. | Milánkovics I | Molecular genetics and metabolism | 2007 | PMID: 17185019 |
| Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations. | Neto EC | Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas | 2004 | PMID: 15060693 |
| Molecular characterisation of 34 patients with biotinidase deficiency ascertained by newborn screening and family investigation. | Mühl A | European journal of human genetics : EJHG | 2001 | PMID: 11313766 |
Text-mined citations for this variant ...
HelpRecord last updated Sep 30, 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.