NM_001370658.1(BTD):c.992del (p.Thr331fs) AND Biotinidase deficiency

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 28, 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:: RCV000021980.11

Allele description [Variation Report for NM_001370658.1(BTD):c.992del (p.Thr331fs)]

NM_001370658.1(BTD):c.992del (p.Thr331fs)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.992del (p.Thr331fs)

HGVS:

NC_000003.12:g.15644908del
NG_008019.3:g.48558del
NM_000060.2:c.1052del
NM_001281723.4:c.992del
NM_001281724.3:c.992del
NM_001281725.3:c.992del
NM_001281726.2:c.*2770delC
NM_001323582.2:c.992del
NM_001370658.1:c.992delMANE SELECT
NM_001370752.1:c.992del
NM_001370753.1:c.399+2851del
NM_001407364.1:c.992del
NM_001407365.1:c.992del
NM_001407366.1:c.992del
NM_001407367.1:c.992del
NM_001407368.1:c.992del
NM_001407369.1:c.992del
NM_001407370.1:c.992del
NM_001407371.1:c.992del
NM_001407372.1:c.992del
NM_001407373.1:c.992del
NM_001407374.1:c.992del
NM_001407375.1:c.992del
NM_001407376.1:c.992del
NM_001407377.1:c.992del
NM_001407378.1:c.992del
NM_001407379.1:c.992del
NM_001407380.1:c.399+2851del
NM_001407398.1:c.399+2851del
NM_001407399.1:c.399+2851del
NM_001407400.1:c.399+2851del
NM_001407401.1:c.399+2851del
NP_001268652.2:p.Thr331fs
NP_001268653.2:p.Thr331fs
NP_001268654.1:p.Thr331fs
NP_001310511.1:p.Thr331fs
NP_001357587.1:p.Thr331fs
NP_001357681.1:p.Thr331fs
NP_001394293.1:p.Thr331fs
NP_001394294.1:p.Thr331fs
NP_001394295.1:p.Thr331fs
NP_001394296.1:p.Thr331fs
NP_001394297.1:p.Thr331fs
NP_001394298.1:p.Thr331fs
NP_001394299.1:p.Thr331fs
NP_001394300.1:p.Thr331fs
NP_001394301.1:p.Thr331fs
NP_001394302.1:p.Thr331fs
NP_001394303.1:p.Thr331fs
NP_001394304.1:p.Thr331fs
NP_001394305.1:p.Thr331fs
NP_001394306.1:p.Thr331fs
NP_001394307.1:p.Thr331fs
NP_001394308.1:p.Thr331fs
NC_000003.11:g.15686415del
NG_008019.2:g.48557del
NM_000060.2:c.1052delC
NM_000060.4:c.1052del
p.Thr351Lysfs*12

Protein change:

T331fs

Links:

dbSNP: rs397514398

NCBI 1000 Genomes Browser:

rs397514398

Molecular consequence:

NM_001281723.4:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281724.3:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281725.3:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001323582.2:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370658.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370752.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407364.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407365.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407366.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407367.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407368.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407369.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407370.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407371.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407372.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407373.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407374.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407375.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407376.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407377.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407378.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407379.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370753.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407380.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407398.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407399.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407400.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407401.1:c.399+2851del - 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
SCV000486792	Counsyl	no assertion criteria provided	Pathogenic (Aug 9, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12359137, 20083419
SCV001235508	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12359137, 15776412, 20083419, 17382128, 19728141, 29359854, 28492532
SCV004211459	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 23, 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

SCV000486792

Counsyl

no assertion criteria provided

Pathogenic
(Aug 9, 2016)

unknown

clinical testing

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

SCV001235508

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 28, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV004211459

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 23, 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	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

Seventeen novel mutations that cause profound biotinidase deficiency.

Wolf B, Jensen K, Hüner G, Demirkol M, Baykal T, Divry P, Rolland MO, Perez-Cerdá C, Ugarte M, Straussberg R, Basel-Vanagaite L, Baumgartner ER, Suormala T, Scholl S, Das AM, Schweitzer S, Pronicka E, Sykut-Cegielska J.

Mol Genet Metab. 2002 Sep-Oct;77(1-2):108-11.

PubMed [citation]

PMID:: 12359137

Biotinidase deficiency: novel mutations and their biochemical and clinical correlates.

Wolf B, Jensen KP, Barshop B, Blitzer M, Carlson M, Goudie DR, Gokcay GH, Demirkol M, Baykal T, Demir F, Quary S, Shih LY, Pedro HF, Chen TH, Slonim AE.

Hum Mutat. 2005 Apr;25(4):413.

PubMed [citation]

PMID:: 15776412

See all PubMed Citations (8)

Details of each submission

From Counsyl, SCV000486792.2

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

#	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, SCV001235508.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Thr351Lysfs*12) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 193 amino acid(s) of the BTD protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with profound biotinidase deficiency (PMID: 12359137, 15776412, 20083419). ClinVar contains an entry for this variant (Variation ID: 25057). 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. For these reasons, this variant has been classified as 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

From Baylor Genetics, SCV004211459.1

#	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 26, 2024

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