NM_001370658.1(BTD):c.383G>A (p.Arg128His) AND Biotinidase deficiency

Germline classification:: Likely pathogenic (5 submissions)
Last evaluated:: Dec 6, 2023
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:: RCV000021924.12

Allele description [Variation Report for NM_001370658.1(BTD):c.383G>A (p.Arg128His)]

NM_001370658.1(BTD):c.383G>A (p.Arg128His)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.383G>A (p.Arg128His)

HGVS:

NC_000003.12:g.15642041G>A
NG_008019.2:g.45690G>A
NM_000060.4:c.443G>A
NM_001281723.4:c.383G>A
NM_001281724.3:c.383G>A
NM_001281725.3:c.383G>A
NM_001281726.3:c.383G>A
NM_001323582.2:c.383G>A
NM_001370658.1:c.383G>AMANE SELECT
NM_001370752.1:c.383G>A
NM_001370753.1:c.383G>A
NM_001407364.1:c.383G>A
NM_001407365.1:c.383G>A
NM_001407366.1:c.383G>A
NM_001407367.1:c.383G>A
NM_001407368.1:c.383G>A
NM_001407369.1:c.383G>A
NM_001407370.1:c.383G>A
NM_001407371.1:c.383G>A
NM_001407372.1:c.383G>A
NM_001407373.1:c.383G>A
NM_001407374.1:c.383G>A
NM_001407375.1:c.383G>A
NM_001407376.1:c.383G>A
NM_001407377.1:c.383G>A
NM_001407378.1:c.383G>A
NM_001407379.1:c.383G>A
NM_001407380.1:c.383G>A
NM_001407381.1:c.446G>A
NM_001407382.1:c.383G>A
NM_001407383.1:c.383G>A
NM_001407384.1:c.383G>A
NM_001407386.1:c.383G>A
NM_001407388.1:c.383G>A
NM_001407390.1:c.383G>A
NM_001407392.1:c.383G>A
NM_001407394.1:c.383G>A
NM_001407395.1:c.383G>A
NM_001407396.1:c.383G>A
NM_001407397.1:c.383G>A
NM_001407398.1:c.383G>A
NM_001407399.1:c.383G>A
NM_001407400.1:c.383G>A
NM_001407401.1:c.383G>A
NP_000051.1:p.Arg148His
NP_001268652.2:p.Arg128His
NP_001268652.2:p.Arg128His
NP_001268653.2:p.Arg128His
NP_001268654.1:p.Arg128His
NP_001268654.1:p.Arg128His
NP_001268655.2:p.Arg128His
NP_001268655.2:p.Arg128His
NP_001310511.1:p.Arg128His
NP_001310511.1:p.Arg128His
NP_001357587.1:p.Arg128His
NP_001357681.1:p.Arg128His
NP_001357682.1:p.Arg128His
NP_001394293.1:p.Arg128His
NP_001394294.1:p.Arg128His
NP_001394295.1:p.Arg128His
NP_001394296.1:p.Arg128His
NP_001394297.1:p.Arg128His
NP_001394298.1:p.Arg128His
NP_001394299.1:p.Arg128His
NP_001394300.1:p.Arg128His
NP_001394301.1:p.Arg128His
NP_001394302.1:p.Arg128His
NP_001394303.1:p.Arg128His
NP_001394304.1:p.Arg128His
NP_001394305.1:p.Arg128His
NP_001394306.1:p.Arg128His
NP_001394307.1:p.Arg128His
NP_001394308.1:p.Arg128His
NP_001394309.1:p.Arg128His
NP_001394310.1:p.Arg149His
NP_001394311.1:p.Arg128His
NP_001394312.1:p.Arg128His
NP_001394313.1:p.Arg128His
NP_001394315.1:p.Arg128His
NP_001394317.1:p.Arg128His
NP_001394319.1:p.Arg128His
NP_001394321.1:p.Arg128His
NP_001394323.1:p.Arg128His
NP_001394324.1:p.Arg128His
NP_001394325.1:p.Arg128His
NP_001394326.1:p.Arg128His
NP_001394327.1:p.Arg128His
NP_001394328.1:p.Arg128His
NP_001394329.1:p.Arg128His
NP_001394330.1:p.Arg128His
NC_000003.11:g.15683548G>A
NM_001281723.3:c.383G>A
NM_001281725.2:c.383G>A
NM_001281726.2:c.383G>A
NM_001323582.1:c.383G>A
NM_001370658.1:c.383G>A

Protein change:

R128H

Links:

dbSNP: rs367902696

NCBI 1000 Genomes Browser:

rs367902696

Molecular consequence:

NM_000060.4:c.443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281726.3:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370752.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370753.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407379.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407380.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407381.1:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407382.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407383.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407384.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407386.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407388.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407390.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407392.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407394.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407395.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407396.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407397.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407398.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407399.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407400.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407401.1:c.383G>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000894297	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001132347	Counsyl	no assertion criteria provided	Uncertain significance (May 17, 2019)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20224900, 20556795
SCV002081550	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Apr 26, 2021)	germline	clinical testing
SCV003280764	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 6, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20224900, 33312878, 28492532
SCV004211403	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 19, 2023)	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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of mutations causing biotinidase deficiency.

Pindolia K, Jordan M, Wolf B.

Hum Mutat. 2010 Sep;31(9):983-91. doi: 10.1002/humu.21303.

PubMed [citation]

PMID:: 20556795

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 (5)

PMC

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, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000894297.1

#	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 Counsyl, SCV001132347.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002081550.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV003280764.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 148 of the BTD protein (p.Arg148His). This variant is present in population databases (rs367902696, gnomAD 0.01%). This missense change has been observed in individuals with biotinidase deficiency (PMID: 20224900, 33312878). ClinVar contains an entry for this variant (Variation ID: 25005). 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 with a positive predictive value of 95%. 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.

#	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 Baylor Genetics, SCV004211403.1

#	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

Last Updated: Feb 20, 2024

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