NM_001370658.1(BTD):c.175C>T (p.Arg59Cys) AND Biotinidase deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (7 submissions)
Last evaluated:: Mar 22, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000001982.13

Allele description

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

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)

Name:: Biotinidase deficiency
Synonyms:: BTD deficiency; Late-onset biotin-responsive multiple carboxylase deficiency; Biotin deficiency
Identifiers:: MONDO: MONDO:0009665; MedGen: C0220754; Orphanet: 79241; OMIM: 253260

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Gene ID:5321

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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	PubMed (1) [See all records that cite this PMID]
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) [See all records that cite these PMIDs] 10801053, 25423671, 20224900 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV001430585	Hadassah Hebrew University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 20, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 33223529
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	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10801053, 27845546, 14707518, 28492532
SCV002803666	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 11, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004211437	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 22, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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
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	yes	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

See all PubMed Citations (8)

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 Invitae, 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: Aug 4, 2024

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