NM_001370658.1(BTD):c.1406A>C (p.Asn469Thr) AND Biotinidase deficiency

Clinical significance:Uncertain significance (Last evaluated: Jan 5, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000001980.5

Allele description [Variation Report for NM_001370658.1(BTD):c.1406A>C (p.Asn469Thr)]

NM_001370658.1(BTD):c.1406A>C (p.Asn469Thr)

Gene:
BTD:biotinidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p25.1
Genomic location:
Preferred name:
NM_001370658.1(BTD):c.1406A>C (p.Asn469Thr)
Other names:
N489T
HGVS:
  • NC_000003.12:g.15645322A>C
  • NG_008019.1:g.48575A>C
  • NG_008019.2:g.48971A>C
  • NM_000060.2:c.1466A>C
  • NM_001281723.3:c.1406A>C
  • NM_001281724.3:c.1406A>C
  • NM_001281725.2:c.1406A>C
  • NM_001323582.1:c.1406A>C
  • NM_001370658.1:c.1406A>CMANE SELECT
  • NM_001370752.1:c.1015+391A>C
  • NM_001370753.1:c.399+3265A>C
  • NP_001268652.2:p.Asn469Thr
  • NP_001268653.2:p.Asn469Thr
  • NP_001268654.1:p.Asn469Thr
  • NP_001310511.1:p.Asn469Thr
  • NP_001357587.1:p.Asn469Thr
  • NC_000003.11:g.15686829A>C
  • c.1466A>C
Protein change:
N469T; ASN489THR
Links:
OMIM: 609019.0008; dbSNP: rs104893692
NCBI 1000 Genomes Browser:
rs104893692
Molecular consequence:
  • NM_001370752.1:c.1015+391A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001370753.1:c.399+3265A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001281723.3:c.1406A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281724.3:c.1406A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281725.2:c.1406A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323582.1:c.1406A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370658.1:c.1406A>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000022138OMIMno assertion criteria providedPathogenic
(Jun 1, 1998)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000042691Research and Development, ARUP Laboratoriesno assertion criteria providedPathogenic
(Feb 17, 2017)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000441834Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000800649Counsylcriteria provided, single submitter
Uncertain significance
(Jan 5, 2018)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedliterature only
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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

Mutation in a putative glycosylation site (N489T) of biotinidase in the only known Japanese child with biotinidase deficiency.

Pomponio RJ, Yamaguchi A, Arashima S, Hymes J, Wolf B.

Mol Genet Metab. 1998 Jun;64(2):152-4.

PubMed [citation]
PMID:
9705240

Details of each submission

From OMIM, SCV000022138.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a Japanese child with biotinidase deficiency (253260) identified in a pilot newborn screening program in Sapporo, Japan, Pomponio et al. (1998) identified a 1466A-C transversion in exon 4 of the BTD gene, resulting in an asn489-to-thr (N489T) substitution in the putative glycosylation site of the BTD protein. The child was treated with oral biotin supplementation from age 2 months to 5 years. Biotin supplementation was then discontinued and the child, who was 8 years old at the time of report, had remained asymptomatic. Hearing and vision testing had been normal. He showed 10.8% of mean normal serum biotinyl-hydrolase activity and trace biotinyl-transferase activity.

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

From Research and Development, ARUP Laboratories, SCV000042691.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000441834.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The BTD c.1466A>C (Asn489Thr) variant has been reported in three studies and was found in a homozygous state in one individual with 10.8% of the mean normal biotinyl hydrolase activity (Pomponio et al. 1998). This individual was also homozygous for an additional polymorphism, and each of the individual's parents was shown to be a heterozygous carrier of both variants. Control data are unavailable for this variant, which is reported at a frequency of 0.00046 in the East Asian population of the Exome Aggregation Consortium. The p.Asn489Thr variant is present in a well-conserved residue and is predicted to abolish a putative N-linked glycosylation site (Pomponio et al. 1998; Pindolia et al. 2010). Based on the evidence, the p.Asn489Thr variant is classified as a variant of unknown significance but suspicious for pathogenicity for biotinidase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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

From Counsyl, SCV000800649.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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