NM_001370658.1(BTD):c.175C>T (p.Arg59Cys) AND Biotinidase deficiency
- Germline classification:
- Pathogenic/Likely pathogenic (7 submissions)
- Last evaluated:
- Mar 22, 2024
- Review status:
- 2 stars out of maximum of 4 starscriteria provided, multiple submitters, no conflicts
- Somatic classification
of clinical impact: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Somatic classification
of oncogenicity: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Record status:
- current
- Accession:
- RCV000001982.14
Allele description [Variation Report for NM_001370658.1(BTD):c.175C>T (p.Arg59Cys)]
NM_001370658.1(BTD):c.175C>T (p.Arg59Cys)
- Gene:
- BTD:biotinidase [Gene - OMIM - HGNC]
- Variant type:
- single nucleotide variant
- Cytogenetic location:
- 3p25.1
- Genomic location:
- Preferred name:
- NM_001370658.1(BTD):c.175C>T (p.Arg59Cys)
- HGVS:
- NC_000003.12:g.15635614C>T
- NG_008019.2:g.39263C>T
- NM_000060.4:c.235C>T
- NM_001281723.4:c.175C>T
- NM_001281724.3:c.175C>T
- NM_001281725.3:c.175C>T
- NM_001281726.3:c.175C>T
- NM_001323582.2:c.175C>T
- NM_001370658.1:c.175C>TMANE SELECT
- NM_001370752.1:c.175C>T
- NM_001370753.1:c.175C>T
- NM_001407364.1:c.175C>T
- NM_001407365.1:c.175C>T
- NM_001407366.1:c.175C>T
- NM_001407367.1:c.175C>T
- NM_001407368.1:c.175C>T
- NM_001407369.1:c.175C>T
- NM_001407370.1:c.175C>T
- NM_001407371.1:c.175C>T
- NM_001407372.1:c.175C>T
- NM_001407373.1:c.175C>T
- NM_001407374.1:c.175C>T
- NM_001407375.1:c.175C>T
- NM_001407376.1:c.175C>T
- NM_001407377.1:c.175C>T
- NM_001407378.1:c.175C>T
- NM_001407379.1:c.175C>T
- NM_001407380.1:c.175C>T
- NM_001407381.1:c.175C>T
- NM_001407382.1:c.175C>T
- NM_001407383.1:c.175C>T
- NM_001407384.1:c.175C>T
- NM_001407386.1:c.175C>T
- NM_001407388.1:c.175C>T
- NM_001407390.1:c.175C>T
- NM_001407392.1:c.175C>T
- NM_001407394.1:c.175C>T
- NM_001407395.1:c.175C>T
- NM_001407396.1:c.175C>T
- NM_001407397.1:c.175C>T
- NM_001407398.1:c.175C>T
- NM_001407399.1:c.175C>T
- NM_001407400.1:c.175C>T
- NM_001407401.1:c.175C>T
- NP_000051.1:p.Arg79Cys
- NP_001268652.2:p.Arg59Cys
- NP_001268652.2:p.Arg59Cys
- NP_001268653.2:p.Arg59Cys
- NP_001268654.1:p.Arg59Cys
- NP_001268654.1:p.Arg59Cys
- NP_001268655.1:p.Arg79Cys
- NP_001268655.2:p.Arg59Cys
- NP_001268655.2:p.Arg59Cys
- NP_001310511.1:p.Arg59Cys
- NP_001310511.1:p.Arg59Cys
- NP_001357587.1:p.Arg59Cys
- NP_001357681.1:p.Arg59Cys
- NP_001357682.1:p.Arg59Cys
- NP_001394293.1:p.Arg59Cys
- NP_001394294.1:p.Arg59Cys
- NP_001394295.1:p.Arg59Cys
- NP_001394296.1:p.Arg59Cys
- NP_001394297.1:p.Arg59Cys
- NP_001394298.1:p.Arg59Cys
- NP_001394299.1:p.Arg59Cys
- NP_001394300.1:p.Arg59Cys
- NP_001394301.1:p.Arg59Cys
- NP_001394302.1:p.Arg59Cys
- NP_001394303.1:p.Arg59Cys
- NP_001394304.1:p.Arg59Cys
- NP_001394305.1:p.Arg59Cys
- NP_001394306.1:p.Arg59Cys
- NP_001394307.1:p.Arg59Cys
- NP_001394308.1:p.Arg59Cys
- NP_001394309.1:p.Arg59Cys
- NP_001394310.1:p.Arg59Cys
- NP_001394311.1:p.Arg59Cys
- NP_001394312.1:p.Arg59Cys
- NP_001394313.1:p.Arg59Cys
- NP_001394315.1:p.Arg59Cys
- NP_001394317.1:p.Arg59Cys
- NP_001394319.1:p.Arg59Cys
- NP_001394321.1:p.Arg59Cys
- NP_001394323.1:p.Arg59Cys
- NP_001394324.1:p.Arg59Cys
- NP_001394325.1:p.Arg59Cys
- NP_001394326.1:p.Arg59Cys
- NP_001394327.1:p.Arg59Cys
- NP_001394328.1:p.Arg59Cys
- NP_001394329.1:p.Arg59Cys
- NP_001394330.1:p.Arg59Cys
- NC_000003.11:g.15677121C>T
- NM_000060.4:c.235C>T
- NM_001281723.3:c.175C>T
- NM_001281725.2:c.175C>T
- NM_001281726.1:c.235C>T
- NM_001281726.2:c.175C>T
- NM_001323582.1:c.175C>T
- c.235C>T
This HGVS expression did not pass validation- Protein change:
- R59C; ARG79CYS
- Links:
- OMIM: 609019.0010; dbSNP: rs104893687
- NCBI 1000 Genomes Browser:
- rs104893687
- Molecular consequence:
- NM_000060.4:c.235C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001281723.4:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001281724.3:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001281725.3:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001281726.3:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001323582.2:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001370658.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001370752.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001370753.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407364.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407365.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407366.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407367.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407368.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407369.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407370.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407371.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407372.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407373.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407374.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407375.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407376.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407377.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407378.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407379.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407380.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407381.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407382.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407383.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407384.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407386.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407388.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407390.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407392.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407394.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407395.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407396.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407397.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407398.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407399.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407400.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001407401.1:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
Condition(s)
Assertion and evidence details
| Submission Accession | Submitter | Review Status (Assertion method) | Clinical Significance (Last evaluated) | Origin | Method | Citations |
|---|---|---|---|---|---|---|
| SCV000022140 | OMIM | no assertion criteria provided | Pathogenic (Mar 1, 2000) | germline | literature only | |
| SCV000487041 | Counsyl | criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015)) | Pathogenic (Sep 28, 2016) | unknown | clinical testing | PubMed (3) mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, |
| SCV001430585 | Hadassah Hebrew University Medical Center | criteria provided, single submitter (ACMG Guidelines, 2015) | Likely pathogenic (Jun 20, 2019) | germline | clinical testing | |
| SCV002073679 | Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence, | no assertion criteria provided | Likely pathogenic | inherited | clinical testing | |
| SCV002236290 | Labcorp Genetics (formerly Invitae), Labcorp | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Pathogenic (Sep 17, 2023) | germline | clinical testing | |
| SCV002803666 | Fulgent Genetics, Fulgent Genetics | criteria provided, single submitter (ACMG Guidelines, 2015) | Pathogenic (Oct 11, 2021) | unknown | clinical testing | |
| SCV004211437 | Baylor Genetics | criteria provided, single submitter (ACMG Guidelines, 2015) | Pathogenic (Mar 22, 2024) | unknown | clinical testing |
Summary from all submissions
| Ethnicity | Origin | Affected | Individuals | Families | Chromosomes tested | Number Tested | Family history | Method |
|---|---|---|---|---|---|---|---|---|
| not provided | germline | yes | not provided | not provided | not provided | not provided | not provided | clinical testing |
| not provided | germline | unknown | not provided | not provided | not provided | not provided | not provided | clinical testing |
| not provided | inherited | yes | not provided | not provided | not provided | not provided | not provided | clinical testing |
| not provided | germline | not provided | not provided | not provided | not provided | not provided | not provided | literature only |
| not provided | unknown | unknown | not provided | not provided | not provided | not provided | not provided | clinical testing |
Citations
PubMed
Mutations in BTD gene causing biotinidase deficiency: a regional report.
Kasapkara ÇS, Akar M, Özbek MN, Tüzün H, Aldudak B, Baran RT, Tanyalçın T.
J Pediatr Endocrinol Metab. 2015 Mar;28(3-4):421-4. doi: 10.1515/jpem-2014-0056.
PubMed [citation]
- PMID:
- 25423671
Profound biotinidase deficiency: a rare disease among native Swedes.
Ohlsson A, Guthenberg C, Holme E, von Döbeln U.
J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S175-80. doi: 10.1007/s10545-010-9065-y. Epub 2010 Mar 12.
PubMed [citation]
- PMID:
- 20224900
Details of each submission
From OMIM, SCV000022140.1
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | literature only | PubMed (1) |
Description
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.
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | germline | not provided | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
From Counsyl, SCV000487041.2
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (3) |
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | unknown | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
From Hadassah Hebrew University Medical Center, SCV001430585.1
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (2) |
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
From Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,, SCV002073679.1
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | inherited | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
From Labcorp Genetics (formerly Invitae), Labcorp, SCV002236290.3
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (4) |
Description
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.
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | germline | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
From Fulgent Genetics, Fulgent Genetics, SCV002803666.1
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | unknown | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
From Baylor Genetics, SCV004211437.2
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | unknown | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
Last Updated: Oct 20, 2024