NM_001370658.1(BTD):c.132G>C (p.Glu44Asp) AND Biotinidase deficiency

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 10, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000032017.7

Allele description

NM_001370658.1(BTD):c.132G>C (p.Glu44Asp)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.132G>C (p.Glu44Asp)

Other names:

E64D

HGVS:

NC_000003.12:g.15635571G>C
NG_008019.2:g.39220G>C
NM_000060.4:c.192G>C
NM_001281723.4:c.132G>C
NM_001281724.3:c.132G>C
NM_001281725.3:c.132G>C
NM_001281726.3:c.132G>C
NM_001323582.2:c.132G>C
NM_001370658.1:c.132G>CMANE SELECT
NM_001370752.1:c.132G>C
NM_001370753.1:c.132G>C
NM_001407364.1:c.132G>C
NM_001407365.1:c.132G>C
NM_001407366.1:c.132G>C
NM_001407367.1:c.132G>C
NM_001407368.1:c.132G>C
NM_001407369.1:c.132G>C
NM_001407370.1:c.132G>C
NM_001407371.1:c.132G>C
NM_001407372.1:c.132G>C
NM_001407373.1:c.132G>C
NM_001407374.1:c.132G>C
NM_001407375.1:c.132G>C
NM_001407376.1:c.132G>C
NM_001407377.1:c.132G>C
NM_001407378.1:c.132G>C
NM_001407379.1:c.132G>C
NM_001407380.1:c.132G>C
NM_001407381.1:c.132G>C
NM_001407382.1:c.132G>C
NM_001407383.1:c.132G>C
NM_001407384.1:c.132G>C
NM_001407386.1:c.132G>C
NM_001407388.1:c.132G>C
NM_001407390.1:c.132G>C
NM_001407392.1:c.132G>C
NM_001407394.1:c.132G>C
NM_001407395.1:c.132G>C
NM_001407396.1:c.132G>C
NM_001407397.1:c.132G>C
NM_001407398.1:c.132G>C
NM_001407399.1:c.132G>C
NM_001407400.1:c.132G>C
NM_001407401.1:c.132G>C
NP_000051.1:p.Glu64Asp
NP_001268652.2:p.Glu44Asp
NP_001268652.2:p.Glu44Asp
NP_001268653.2:p.Glu44Asp
NP_001268654.1:p.Glu44Asp
NP_001268654.1:p.Glu44Asp
NP_001268655.2:p.Glu44Asp
NP_001268655.2:p.Glu44Asp
NP_001310511.1:p.Glu44Asp
NP_001310511.1:p.Glu44Asp
NP_001357587.1:p.Glu44Asp
NP_001357681.1:p.Glu44Asp
NP_001357682.1:p.Glu44Asp
NP_001394293.1:p.Glu44Asp
NP_001394294.1:p.Glu44Asp
NP_001394295.1:p.Glu44Asp
NP_001394296.1:p.Glu44Asp
NP_001394297.1:p.Glu44Asp
NP_001394298.1:p.Glu44Asp
NP_001394299.1:p.Glu44Asp
NP_001394300.1:p.Glu44Asp
NP_001394301.1:p.Glu44Asp
NP_001394302.1:p.Glu44Asp
NP_001394303.1:p.Glu44Asp
NP_001394304.1:p.Glu44Asp
NP_001394305.1:p.Glu44Asp
NP_001394306.1:p.Glu44Asp
NP_001394307.1:p.Glu44Asp
NP_001394308.1:p.Glu44Asp
NP_001394309.1:p.Glu44Asp
NP_001394310.1:p.Glu44Asp
NP_001394311.1:p.Glu44Asp
NP_001394312.1:p.Glu44Asp
NP_001394313.1:p.Glu44Asp
NP_001394315.1:p.Glu44Asp
NP_001394317.1:p.Glu44Asp
NP_001394319.1:p.Glu44Asp
NP_001394321.1:p.Glu44Asp
NP_001394323.1:p.Glu44Asp
NP_001394324.1:p.Glu44Asp
NP_001394325.1:p.Glu44Asp
NP_001394326.1:p.Glu44Asp
NP_001394327.1:p.Glu44Asp
NP_001394328.1:p.Glu44Asp
NP_001394329.1:p.Glu44Asp
NP_001394330.1:p.Glu44Asp
NC_000003.11:g.15677078G>C
NM_001281723.3:c.132G>C
NM_001281724.1:c.198G>C
NM_001281725.2:c.132G>C
NM_001281726.2:c.132G>C
NM_001323582.1:c.132G>C

Protein change:

E44D

Links:

dbSNP: rs397514436

NCBI 1000 Genomes Browser:

rs397514436

Molecular consequence:

NM_000060.4:c.192G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281726.3:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370752.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370753.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407379.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407380.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407381.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407382.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407383.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407384.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407386.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407388.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407390.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407392.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407394.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407395.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407396.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407397.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407398.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407399.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407400.1:c.132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407401.1:c.132G>C - 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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cilia- and flagella-associated protein 221 isoform X4 [Homo sapiens]
cilia- and flagella-associated protein 221 isoform X4 [Homo sapiens]
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001514641	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12359137, 26810761, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001514641

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 10, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Citations

PubMed

Seventeen novel mutations that cause profound biotinidase deficiency.

Wolf B, Jensen K, Hüner G, Demirkol M, Baykal T, Divry P, Rolland MO, Perez-Cerdá C, Ugarte M, Straussberg R, Basel-Vanagaite L, Baumgartner ER, Suormala T, Scholl S, Das AM, Schweitzer S, Pronicka E, Sykut-Cegielska J.

Mol Genet Metab. 2002 Sep-Oct;77(1-2):108-11.

PubMed [citation]

PMID:: 12359137

Forty-eight novel mutations causing biotinidase deficiency.

Procter M, Wolf B, Mao R.

Mol Genet Metab. 2016 Mar;117(3):369-72. doi: 10.1016/j.ymgme.2016.01.002. Epub 2016 Jan 12.

PubMed [citation]

PMID:: 26810761

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001514641.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu64 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 12359137), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 38574). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 26810761; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 64 of the BTD protein (p.Glu64Asp).

#	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

Last Updated: Feb 20, 2024

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