NM_001370658.1(BTD):c.1271A>G (p.Asp424Gly) AND Biotinidase deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 28, 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:: RCV001904240.8

Allele description [Variation Report for NM_001370658.1(BTD):c.1271A>G (p.Asp424Gly)]

NM_001370658.1(BTD):c.1271A>G (p.Asp424Gly)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.1271A>G (p.Asp424Gly)

HGVS:

NC_000003.12:g.15645187A>G
NG_008019.2:g.48836A>G
NG_008019.3:g.48837A>G
NM_000060.4:c.1331A>G
NM_001281723.4:c.1271A>G
NM_001281724.3:c.1271A>G
NM_001281725.3:c.1271A>G
NM_001323582.2:c.1271A>G
NM_001370658.1:c.1271A>GMANE SELECT
NM_001370752.1:c.1015+256A>G
NM_001370753.1:c.399+3130A>G
NM_001407364.1:c.1271A>G
NM_001407365.1:c.1271A>G
NM_001407366.1:c.1271A>G
NM_001407367.1:c.1271A>G
NM_001407368.1:c.1271A>G
NM_001407369.1:c.1271A>G
NM_001407370.1:c.1271A>G
NM_001407371.1:c.1271A>G
NM_001407372.1:c.1271A>G
NM_001407373.1:c.1271A>G
NM_001407374.1:c.1271A>G
NM_001407375.1:c.1271A>G
NM_001407376.1:c.1271A>G
NM_001407377.1:c.1271A>G
NM_001407378.1:c.1271A>G
NP_000051.1:p.Asp444Gly
NP_001268652.2:p.Asp424Gly
NP_001268652.2:p.Asp424Gly
NP_001268653.2:p.Asp424Gly
NP_001268654.1:p.Asp424Gly
NP_001268654.1:p.Asp424Gly
NP_001310511.1:p.Asp424Gly
NP_001310511.1:p.Asp424Gly
NP_001357587.1:p.Asp424Gly
NP_001394293.1:p.Asp424Gly
NP_001394294.1:p.Asp424Gly
NP_001394295.1:p.Asp424Gly
NP_001394296.1:p.Asp424Gly
NP_001394297.1:p.Asp424Gly
NP_001394298.1:p.Asp424Gly
NP_001394299.1:p.Asp424Gly
NP_001394300.1:p.Asp424Gly
NP_001394301.1:p.Asp424Gly
NP_001394302.1:p.Asp424Gly
NP_001394303.1:p.Asp424Gly
NP_001394304.1:p.Asp424Gly
NP_001394305.1:p.Asp424Gly
NP_001394306.1:p.Asp424Gly
NP_001394307.1:p.Asp424Gly
NC_000003.11:g.15686694A>G
NM_001281723.3:c.1271A>G
NM_001281725.2:c.1271A>G
NM_001323582.1:c.1271A>G

Protein change:

D424G

Links:

dbSNP: rs2065662435

NCBI 1000 Genomes Browser:

rs2065662435

Molecular consequence:

NM_001370752.1:c.1015+256A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001370753.1:c.399+3130A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000060.4:c.1331A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.1271A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.1271A>G - 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

Recent activity

Clear Turn Off Turn On

apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B [Macaca mulat...
apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B [Macaca mulatta]
gi|334382967|gb|AEG79277.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002122807	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 28, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9654207, 10206677, 12227467, 23644139, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002122807

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 28, 2023)

germline

clinical testing

PubMed (5)
[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

Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene.

Swango KL, Demirkol M, Hüner G, Pronicka E, Sykut-Cegielska J, Schulze A, Mayatepek E, Wolf B.

Hum Genet. 1998 May;102(5):571-5. Erratum in: Hum Genet 1998 Jun;102(6):712.

PubMed [citation]

PMID:: 9654207

Double mutation (A171T and D444H) is a common cause of profound biotinidase deficiency in children ascertained by newborn screening the the United States. Mutations in brief no. 128. Online.

Norrgard KJ, Pomponio RJ, Swango KL, Hymes J, Reynolds T, Buck GA, Wolf B.

Hum Mutat. 1998;11(5):410.

PubMed [citation]

PMID:: 10206677

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002122807.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 444 of the BTD protein (p.Asp444Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 1358756). 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%. This variant disrupts the p.Asp444 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9654207, 10206677, 12227467, 23644139). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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

Last Updated: Feb 28, 2024

ClinVar

Relating variation to medicine