NM_001370658.1(BTD):c.1350dup (p.Cys451fs) AND Biotinidase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 15, 2022
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:: RCV000411318.10

Allele description [Variation Report for NM_001370658.1(BTD):c.1350dup (p.Cys451fs)]

NM_001370658.1(BTD):c.1350dup (p.Cys451fs)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.1350dup (p.Cys451fs)

HGVS:

NC_000003.12:g.15645266dup
NG_008019.2:g.48915dup
NG_008019.3:g.48916dup
NM_001281723.4:c.1350dup
NM_001281724.3:c.1350dup
NM_001281725.3:c.1350dup
NM_001281726.2:c.*3128dup
NM_001323582.2:c.1350dup
NM_001370658.1:c.1350dupMANE SELECT
NM_001370752.1:c.1015+335dup
NM_001370753.1:c.399+3209dup
NM_001407364.1:c.1350dup
NM_001407365.1:c.1350dup
NM_001407366.1:c.1350dup
NM_001407367.1:c.1350dup
NM_001407368.1:c.1350dup
NM_001407369.1:c.1350dup
NM_001407370.1:c.1350dup
NM_001407371.1:c.1350dup
NM_001407372.1:c.1350dup
NM_001407373.1:c.1350dup
NM_001407374.1:c.1350dup
NM_001407375.1:c.1350dup
NM_001407376.1:c.1350dup
NM_001407377.1:c.1350dup
NM_001407378.1:c.1350dup
NM_001407379.1:c.1015+335dup
NM_001407380.1:c.399+3209dup
NM_001407398.1:c.399+3209dup
NM_001407399.1:c.399+3209dup
NM_001407400.1:c.399+3209dup
NM_001407401.1:c.399+3209dup
NP_001268652.2:p.Cys451fs
NP_001268653.2:p.Cys451fs
NP_001268654.1:p.Cys451fs
NP_001310511.1:p.Cys451fs
NP_001357587.1:p.Cys451fs
NP_001394293.1:p.Cys451fs
NP_001394294.1:p.Cys451fs
NP_001394295.1:p.Cys451fs
NP_001394296.1:p.Cys451fs
NP_001394297.1:p.Cys451fs
NP_001394298.1:p.Cys451fs
NP_001394299.1:p.Cys451fs
NP_001394300.1:p.Cys451fs
NP_001394301.1:p.Cys451fs
NP_001394302.1:p.Cys451fs
NP_001394303.1:p.Cys451fs
NP_001394304.1:p.Cys451fs
NP_001394305.1:p.Cys451fs
NP_001394306.1:p.Cys451fs
NP_001394307.1:p.Cys451fs
NC_000003.11:g.15686771_15686772insC
NC_000003.11:g.15686773dup
NM_000060.3:c.1410dup

Protein change:

C451fs

Links:

dbSNP: rs886041559

NCBI 1000 Genomes Browser:

rs886041559

Molecular consequence:

NM_001281723.4:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281724.3:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281725.3:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001323582.2:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370658.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407364.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407365.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407366.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407367.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407368.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407369.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407370.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407371.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407372.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407373.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407374.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407375.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407376.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407377.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407378.1:c.1350dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370752.1:c.1015+335dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001370753.1:c.399+3209dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001407379.1:c.1015+335dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001407380.1:c.399+3209dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001407398.1:c.399+3209dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001407399.1:c.399+3209dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001407400.1:c.399+3209dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001407401.1:c.399+3209dup - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000486858	Counsyl	no assertion criteria provided	Likely pathogenic (Aug 24, 2016)	unknown	clinical testing
SCV001198039	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 15, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17382128, 19728141, 29359854, 31618753, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000486858

Counsyl

no assertion criteria provided

Likely pathogenic
(Aug 24, 2016)

unknown

clinical testing

SCV001198039

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 15, 2022)

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hearing loss in biotinidase deficiency: genotype-phenotype correlation.

Sivri HS, Genç GA, Tokatli A, Dursun A, Coşkun T, Aydin HI, Sennaroğlu L, Belgin E, Jensen K, Wolf B.

J Pediatr. 2007 Apr;150(4):439-42. Erratum in: J Pediatr. 2007 Aug;151(2):222. Tokatlý, Ayşegül [corrected to Tokatli, Ayşegül]; Aydýn, Halil Ybrahim [corrected to Aydin, Halil Ibrahim].

PubMed [citation]

PMID:: 17382128

Diagnosis, treatment, follow-up and gene mutation analysis in four Chinese children with biotinidase deficiency.

Ye J, Wang T, Han LS, Qiu WJ, Zhang HW, Zhang YF, Gao XL, Wang Y, Gu XF.

J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S295-302. doi: 10.1007/s10545-009-1238-1. Epub 2009 Aug 29.

PubMed [citation]

PMID:: 19728141

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000486858.2

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001198039.5

#	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 creates a premature translational stop signal (p.Cys471Leufs*13) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 73 amino acid(s) of the BTD protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BTD protein in which other variant(s) (p.Leu498Phefs*13) have been determined to be pathogenic (PMID: 17382128, 19728141, 29359854). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 280333). This premature translational stop signal has been observed in individual(s) with BTD-related conditions (PMID: 31618753). This variant is not present in population databases (gnomAD no frequency).

#	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: Nov 3, 2024

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