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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

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002122807Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 28, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024