This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 79 of the BTD protein (p.Arg79Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 10801053, 27845546). ClinVar contains an entry for this variant (Variation ID: 1905). 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 disrupts the p.Arg79 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14707518). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.175C>T (p.Arg59Cys)
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.
(8)
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.
Pathogenic/Likely pathogenic
8
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001370658.1(BTD):c.175C>T (p.Arg59Cys)
Variation ID: 1905 Accession: VCV000001905.33
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3p25.1 3: 15635614 (GRCh38) [ NCBI UCSC ] 3: 15677121 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 20, 2024 Mar 22, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370658.1:c.175C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Arg59Cys missense NM_000060.4:c.235C>T NP_000051.1:p.Arg79Cys missense NM_001281723.4:c.175C>T NP_001268652.2:p.Arg59Cys missense NM_001281724.3:c.175C>T NP_001268653.2:p.Arg59Cys missense NM_001281725.3:c.175C>T NP_001268654.1:p.Arg59Cys missense NM_001281726.3:c.175C>T NP_001268655.2:p.Arg59Cys missense NM_001323582.2:c.175C>T NP_001310511.1:p.Arg59Cys missense NM_001370752.1:c.175C>T NP_001357681.1:p.Arg59Cys missense NM_001370753.1:c.175C>T NP_001357682.1:p.Arg59Cys missense NM_001407364.1:c.175C>T NP_001394293.1:p.Arg59Cys missense NM_001407365.1:c.175C>T NP_001394294.1:p.Arg59Cys missense NM_001407366.1:c.175C>T NP_001394295.1:p.Arg59Cys missense NM_001407367.1:c.175C>T NP_001394296.1:p.Arg59Cys missense NM_001407368.1:c.175C>T NP_001394297.1:p.Arg59Cys missense NM_001407369.1:c.175C>T NP_001394298.1:p.Arg59Cys missense NM_001407370.1:c.175C>T NP_001394299.1:p.Arg59Cys missense NM_001407371.1:c.175C>T NP_001394300.1:p.Arg59Cys missense NM_001407372.1:c.175C>T NP_001394301.1:p.Arg59Cys missense NM_001407373.1:c.175C>T NP_001394302.1:p.Arg59Cys missense NM_001407374.1:c.175C>T NP_001394303.1:p.Arg59Cys missense NM_001407375.1:c.175C>T NP_001394304.1:p.Arg59Cys missense NM_001407376.1:c.175C>T NP_001394305.1:p.Arg59Cys missense NM_001407377.1:c.175C>T NP_001394306.1:p.Arg59Cys missense NM_001407378.1:c.175C>T NP_001394307.1:p.Arg59Cys missense NM_001407379.1:c.175C>T NP_001394308.1:p.Arg59Cys missense NM_001407380.1:c.175C>T NP_001394309.1:p.Arg59Cys missense NM_001407381.1:c.175C>T NP_001394310.1:p.Arg59Cys missense NM_001407382.1:c.175C>T NP_001394311.1:p.Arg59Cys missense NM_001407383.1:c.175C>T NP_001394312.1:p.Arg59Cys missense NM_001407384.1:c.175C>T NP_001394313.1:p.Arg59Cys missense NM_001407386.1:c.175C>T NP_001394315.1:p.Arg59Cys missense NM_001407388.1:c.175C>T NP_001394317.1:p.Arg59Cys missense NM_001407390.1:c.175C>T NP_001394319.1:p.Arg59Cys missense NM_001407392.1:c.175C>T NP_001394321.1:p.Arg59Cys missense NM_001407394.1:c.175C>T NP_001394323.1:p.Arg59Cys missense NM_001407395.1:c.175C>T NP_001394324.1:p.Arg59Cys missense NM_001407396.1:c.175C>T NP_001394325.1:p.Arg59Cys missense NM_001407397.1:c.175C>T NP_001394326.1:p.Arg59Cys missense NM_001407398.1:c.175C>T NP_001394327.1:p.Arg59Cys missense NM_001407399.1:c.175C>T NP_001394328.1:p.Arg59Cys missense NM_001407400.1:c.175C>T NP_001394329.1:p.Arg59Cys missense NM_001407401.1:c.175C>T NP_001394330.1:p.Arg59Cys missense NC_000003.12:g.15635614C>T NC_000003.11:g.15677121C>T NG_008019.2:g.39263C>T - Protein change
- R79C, R59C
- Other names
- -
- Canonical SPDI
- NC_000003.12:15635613:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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 |
670 | 756 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Mar 22, 2024 | RCV000001982.14 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Dec 1, 2021 | RCV001815158.21 |
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. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Jun 20, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: yes
Allele origin:
germline
|
Hadassah Hebrew University Medical Center
Accession: SCV001430585.1
First in ClinVar: Aug 24, 2020 Last updated: Aug 24, 2020 |
|
|
|
Pathogenic
(Oct 11, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002803666.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Sep 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002236290.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 79 of the BTD protein … (more)
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 79 of the BTD protein (p.Arg79Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 10801053, 27845546). ClinVar contains an entry for this variant (Variation ID: 1905). 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 disrupts the p.Arg79 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14707518). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Mar 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004211437.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Sep 28, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000487041.2
First in ClinVar: Apr 04, 2013 Last updated: Dec 24, 2022 |
|
|
|
Likely pathogenic
(Dec 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002062442.20
First in ClinVar: Jan 29, 2022 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Mar 01, 2000)
|
no assertion criteria provided
Method: literature only
|
BIOTINIDASE DEFICIENCY
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022140.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In Turkish children with biotinidase deficiency (253260) identified both clinically and by newborn screening, Pomponio et al. (2000) identified a 235C-T transition in the BTD … (more)
In Turkish children with biotinidase deficiency (253260) identified both clinically and by newborn screening, Pomponio et al. (2000) identified a 235C-T transition in the BTD gene, resulting in an arg79-to-cys (R79C) substitution. Some patients were homozygous and some compound heterozygous. (less)
|
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Biotinidase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
|
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,
Accession: SCV002073679.1
First in ClinVar: Feb 08, 2022 Last updated: Feb 08, 2022 |
|
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 sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 79 of the BTD protein (p.Arg79Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 10801053, 27845546). ClinVar contains an entry for this variant (Variation ID: 1905). 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 disrupts the p.Arg79 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14707518). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Parental exome analysis identifies shared carrier status for a second recessive disorder in couples with an affected child. | Mor-Shaked H | European journal of human genetics : EJHG | 2021 | PMID: 33223529 |
| Clinical, Biochemical and Genetic Analysis of Biotinidase Deficiency in Iranian Population. | Asgari A | Archives of Iranian medicine | 2016 | PMID: 27845546 |
| Mutations in BTD gene causing biotinidase deficiency: a regional report. | Kasapkara ÇS | Journal of pediatric endocrinology & metabolism : JPEM | 2015 | PMID: 25423671 |
| Profound biotinidase deficiency: a rare disease among native Swedes. | Ohlsson A | Journal of inherited metabolic disease | 2010 | PMID: 20224900 |
| Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies. | László A | Journal of inherited metabolic disease | 2003 | PMID: 14707518 |
| Novel mutations cause biotinidase deficiency in Turkish children. | Pomponio RJ | Journal of inherited metabolic disease | 2000 | PMID: 10801053 |
Text-mined citations for rs104893687 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 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.