NM_001370658.1(BTD):c.1419del (p.Tyr474fs) AND Biotinidase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 7, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000696396.9

Allele description [Variation Report for NM_001370658.1(BTD):c.1419del (p.Tyr474fs)]

NM_001370658.1(BTD):c.1419del (p.Tyr474fs)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.1419del (p.Tyr474fs)

HGVS:

NC_000003.12:g.15645335del
NG_008019.3:g.48985del
NM_000060.4:c.1479del
NM_001281723.4:c.1419del
NM_001281724.3:c.1419del
NM_001281725.3:c.1419del
NM_001281726.2:c.*3197delC
NM_001323582.2:c.1419del
NM_001370658.1:c.1419delMANE SELECT
NM_001370752.1:c.1015+404del
NM_001370753.1:c.399+3278del
NM_001407364.1:c.1419del
NM_001407365.1:c.1419del
NM_001407366.1:c.1419del
NM_001407367.1:c.1419del
NM_001407368.1:c.1419del
NM_001407369.1:c.1419del
NM_001407370.1:c.1419del
NM_001407371.1:c.1419del
NM_001407372.1:c.1419del
NM_001407373.1:c.1419del
NM_001407374.1:c.1419del
NM_001407375.1:c.1419del
NM_001407376.1:c.1419del
NM_001407377.1:c.1419del
NM_001407378.1:c.1419del
NM_001407379.1:c.1015+404del
NM_001407380.1:c.399+3278del
NM_001407398.1:c.399+3278del
NM_001407399.1:c.399+3278del
NM_001407400.1:c.399+3278del
NM_001407401.1:c.399+3278del
NP_001268652.2:p.Tyr474fs
NP_001268653.2:p.Tyr474fs
NP_001268654.1:p.Tyr474fs
NP_001310511.1:p.Tyr474fs
NP_001357587.1:p.Tyr474fs
NP_001394293.1:p.Tyr474fs
NP_001394294.1:p.Tyr474fs
NP_001394295.1:p.Tyr474fs
NP_001394296.1:p.Tyr474fs
NP_001394297.1:p.Tyr474fs
NP_001394298.1:p.Tyr474fs
NP_001394299.1:p.Tyr474fs
NP_001394300.1:p.Tyr474fs
NP_001394301.1:p.Tyr474fs
NP_001394302.1:p.Tyr474fs
NP_001394303.1:p.Tyr474fs
NP_001394304.1:p.Tyr474fs
NP_001394305.1:p.Tyr474fs
NP_001394306.1:p.Tyr474fs
NP_001394307.1:p.Tyr474fs
NC_000003.11:g.15686841del
NC_000003.11:g.15686842del
NG_008019.2:g.48984del

Protein change:

Y474fs

Links:

dbSNP: rs1559600938

NCBI 1000 Genomes Browser:

rs1559600938

Molecular consequence:

NM_001281723.4:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281724.3:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281725.3:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001323582.2:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370658.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407364.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407365.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407366.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407367.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407368.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407369.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407370.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407371.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407372.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407373.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407374.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407375.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407376.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407377.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407378.1:c.1419del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370752.1:c.1015+404del - intron variant - [Sequence Ontology: SO:0001627]
NM_001370753.1:c.399+3278del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407379.1:c.1015+404del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407380.1:c.399+3278del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407398.1:c.399+3278del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407399.1:c.399+3278del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407400.1:c.399+3278del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407401.1:c.399+3278del - 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
SCV000824957	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 9, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17382128, 28492532
SCV004211414	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 7, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000824957

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 9, 2017)

germline

clinical testing

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

SCV004211414

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 7, 2023)

unknown

clinical testing

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

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
not provided	unknown	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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000824957.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Leu498Phefs*13) that lies downstream of this variant has been determined to be pathogenic (PMID: 17382128). This suggests that deletion of this region of the BTD protein is causative of disease. This variant has not been reported in the literature in individuals with BTD-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the BTD gene (p.Tyr494Ilefs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 50 amino acids of the BTD protein.

#	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

From Baylor Genetics, SCV004211414.1

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

#	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

Last Updated: Oct 13, 2024

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