NM_001370658.1(BTD):c.754T>G (p.Trp252Gly) AND Biotinidase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 3, 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:: RCV000021965.9

Allele description [Variation Report for NM_001370658.1(BTD):c.754T>G (p.Trp252Gly)]

NM_001370658.1(BTD):c.754T>G (p.Trp252Gly)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.754T>G (p.Trp252Gly)

HGVS:

NC_000003.12:g.15644670T>G
NG_008019.2:g.48319T>G
NG_008019.3:g.48320T>G
NM_000060.4:c.814T>G
NM_001281723.4:c.754T>G
NM_001281724.3:c.754T>G
NM_001281725.3:c.754T>G
NM_001323582.2:c.754T>G
NM_001370658.1:c.754T>GMANE SELECT
NM_001370752.1:c.754T>G
NM_001370753.1:c.399+2613T>G
NM_001407364.1:c.754T>G
NM_001407365.1:c.754T>G
NM_001407366.1:c.754T>G
NM_001407367.1:c.754T>G
NM_001407368.1:c.754T>G
NM_001407369.1:c.754T>G
NM_001407370.1:c.754T>G
NM_001407371.1:c.754T>G
NM_001407372.1:c.754T>G
NM_001407373.1:c.754T>G
NM_001407374.1:c.754T>G
NM_001407375.1:c.754T>G
NM_001407376.1:c.754T>G
NM_001407377.1:c.754T>G
NM_001407378.1:c.754T>G
NM_001407379.1:c.754T>G
NP_000051.1:p.Trp272Gly
NP_001268652.2:p.Trp252Gly
NP_001268652.2:p.Trp252Gly
NP_001268653.2:p.Trp252Gly
NP_001268654.1:p.Trp252Gly
NP_001268654.1:p.Trp252Gly
NP_001310511.1:p.Trp252Gly
NP_001310511.1:p.Trp252Gly
NP_001357587.1:p.Trp252Gly
NP_001357681.1:p.Trp252Gly
NP_001394293.1:p.Trp252Gly
NP_001394294.1:p.Trp252Gly
NP_001394295.1:p.Trp252Gly
NP_001394296.1:p.Trp252Gly
NP_001394297.1:p.Trp252Gly
NP_001394298.1:p.Trp252Gly
NP_001394299.1:p.Trp252Gly
NP_001394300.1:p.Trp252Gly
NP_001394301.1:p.Trp252Gly
NP_001394302.1:p.Trp252Gly
NP_001394303.1:p.Trp252Gly
NP_001394304.1:p.Trp252Gly
NP_001394305.1:p.Trp252Gly
NP_001394306.1:p.Trp252Gly
NP_001394307.1:p.Trp252Gly
NP_001394308.1:p.Trp252Gly
NC_000003.11:g.15686177T>G
NM_001281723.3:c.754T>G
NM_001281725.2:c.754T>G
NM_001323582.1:c.754T>G

Protein change:

W252G

Links:

dbSNP: rs397514387

NCBI 1000 Genomes Browser:

rs397514387

Molecular consequence:

NM_001370753.1:c.399+2613T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000060.4:c.814T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370752.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.754T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407379.1:c.754T>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001212166	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22698809, 28492532
SCV004211487	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 7, 2022)	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

SCV001212166

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 3, 2023)

germline

clinical testing

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

SCV004211487

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 7, 2022)

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

Increased incidence of profound biotinidase deficiency among Hispanic newborns in California.

Cowan TM, Kazerouni NN, Dharajiya N, Lorey F, Roberson M, Hodgkinson C, Schrijver I.

Mol Genet Metab. 2012 Aug;106(4):485-7. doi: 10.1016/j.ymgme.2012.05.017. Epub 2012 May 30.

PubMed [citation]

PMID:: 22698809

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001212166.5

#	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BTD protein function. ClinVar contains an entry for this variant (Variation ID: 25043). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 22698809; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs397514387, gnomAD 0.006%). This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 272 of the BTD protein (p.Trp272Gly).

#	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, SCV004211487.1

#	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: Feb 20, 2024

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