NM_001370658.1(BTD):c.1036_1037dup (p.Gly347fs) AND Biotinidase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 10, 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:: RCV003475096.3

Allele description [Variation Report for NM_001370658.1(BTD):c.1036_1037dup (p.Gly347fs)]

NM_001370658.1(BTD):c.1036_1037dup (p.Gly347fs)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.1036_1037dup (p.Gly347fs)

HGVS:

NC_000003.12:g.15644952_15644953dup
NG_008019.2:g.48601_48602dup
NG_008019.3:g.48602_48603dup
NM_000060.4:c.1096_1097dup
NM_001281723.4:c.1036_1037dup
NM_001281724.3:c.1036_1037dup
NM_001281725.3:c.1036_1037dup
NM_001323582.2:c.1036_1037dup
NM_001370658.1:c.1036_1037dupMANE SELECT
NM_001370752.1:c.1015+21_1015+22dup
NM_001370753.1:c.399+2895_399+2896dup
NM_001407364.1:c.1036_1037dup
NM_001407365.1:c.1036_1037dup
NM_001407366.1:c.1036_1037dup
NM_001407367.1:c.1036_1037dup
NM_001407368.1:c.1036_1037dup
NM_001407369.1:c.1036_1037dup
NM_001407370.1:c.1036_1037dup
NM_001407371.1:c.1036_1037dup
NM_001407372.1:c.1036_1037dup
NM_001407373.1:c.1036_1037dup
NM_001407374.1:c.1036_1037dup
NM_001407375.1:c.1036_1037dup
NM_001407376.1:c.1036_1037dup
NM_001407377.1:c.1036_1037dup
NM_001407378.1:c.1036_1037dup
NP_000051.1:p.Gly367Glnfs
NP_001268652.2:p.Gly347Glnfs
NP_001268652.2:p.Gly347fs
NP_001268653.2:p.Gly347fs
NP_001268654.1:p.Gly347Glnfs
NP_001268654.1:p.Gly347fs
NP_001310511.1:p.Gly347Glnfs
NP_001310511.1:p.Gly347fs
NP_001357587.1:p.Gly347fs
NP_001394293.1:p.Gly347Glnfs
NP_001394294.1:p.Gly347Glnfs
NP_001394295.1:p.Gly347Glnfs
NP_001394296.1:p.Gly347Glnfs
NP_001394297.1:p.Gly347Glnfs
NP_001394298.1:p.Gly347Glnfs
NP_001394299.1:p.Gly347Glnfs
NP_001394300.1:p.Gly347Glnfs
NP_001394301.1:p.Gly347Glnfs
NP_001394302.1:p.Gly347Glnfs
NP_001394303.1:p.Gly347Glnfs
NP_001394304.1:p.Gly347Glnfs
NP_001394305.1:p.Gly347Glnfs
NP_001394306.1:p.Gly347Glnfs
NP_001394307.1:p.Gly347Glnfs
NC_000003.11:g.15686458_15686459insTC
NC_000003.11:g.15686459_15686460dup
NM_001281723.3:c.1036_1037dup
NM_001281725.2:c.1036_1037dup
NM_001323582.1:c.1036_1037dup

Protein change:

G347fs

Links:

dbSNP: rs1004027979

NCBI 1000 Genomes Browser:

rs1004027979

Molecular consequence:

NM_000060.4:c.1096_1097dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281723.4:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281724.3:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281725.3:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001323582.2:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370658.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407364.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407365.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407366.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407367.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407368.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407369.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407370.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407371.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407372.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407373.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407374.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407375.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407376.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407377.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407378.1:c.1036_1037dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370752.1:c.1015+21_1015+22dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001370753.1:c.399+2895_399+2896dup - 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
SCV004211439	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 28, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004293422	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 10, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26810761, 17382128, 19728141, 29359854, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004211439

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 28, 2023)

unknown

clinical testing

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

SCV004293422

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 10, 2023)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Forty-eight novel mutations causing biotinidase deficiency.

Procter M, Wolf B, Mao R.

Mol Genet Metab. 2016 Mar;117(3):369-72. doi: 10.1016/j.ymgme.2016.01.002. Epub 2016 Jan 12.

PubMed [citation]

PMID:: 26810761

See all PubMed Citations (6)

Details of each submission

From Baylor Genetics, SCV004211439.1

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004293422.1

#	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.Gly367Glnfs*23) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 177 amino acid(s) of the BTD protein. This variant is present in population databases (no rsID available, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with biotinidase deficiency (PMID: 26810761). ClinVar contains an entry for this variant (Variation ID: 1330018). 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

Last Updated: Oct 8, 2024

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