NM_001370658.1(BTD):c.622G>T (p.Asp208Tyr) AND Biotinidase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 17, 2024
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:: RCV003473119.4

Allele description [Variation Report for NM_001370658.1(BTD):c.622G>T (p.Asp208Tyr)]

NM_001370658.1(BTD):c.622G>T (p.Asp208Tyr)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.622G>T (p.Asp208Tyr)

Other names:

p.D228Y:GAT>TAT

HGVS:

NC_000003.12:g.15644538G>T
NG_008019.2:g.48187G>T
NG_008019.3:g.48188G>T
NM_000060.4:c.682G>T
NM_001281723.4:c.622G>T
NM_001281724.3:c.622G>T
NM_001281725.3:c.622G>T
NM_001323582.2:c.622G>T
NM_001370658.1:c.622G>TMANE SELECT
NM_001370752.1:c.622G>T
NM_001370753.1:c.399+2481G>T
NM_001407364.1:c.622G>T
NM_001407365.1:c.622G>T
NM_001407366.1:c.622G>T
NM_001407367.1:c.622G>T
NM_001407368.1:c.622G>T
NM_001407369.1:c.622G>T
NM_001407370.1:c.622G>T
NM_001407371.1:c.622G>T
NM_001407372.1:c.622G>T
NM_001407373.1:c.622G>T
NM_001407374.1:c.622G>T
NM_001407375.1:c.622G>T
NM_001407376.1:c.622G>T
NM_001407377.1:c.622G>T
NM_001407378.1:c.622G>T
NM_001407379.1:c.622G>T
NP_000051.1:p.Asp228Tyr
NP_001268652.2:p.Asp208Tyr
NP_001268652.2:p.Asp208Tyr
NP_001268653.2:p.Asp208Tyr
NP_001268654.1:p.Asp208Tyr
NP_001268654.1:p.Asp208Tyr
NP_001310511.1:p.Asp208Tyr
NP_001310511.1:p.Asp208Tyr
NP_001357587.1:p.Asp208Tyr
NP_001357681.1:p.Asp208Tyr
NP_001394293.1:p.Asp208Tyr
NP_001394294.1:p.Asp208Tyr
NP_001394295.1:p.Asp208Tyr
NP_001394296.1:p.Asp208Tyr
NP_001394297.1:p.Asp208Tyr
NP_001394298.1:p.Asp208Tyr
NP_001394299.1:p.Asp208Tyr
NP_001394300.1:p.Asp208Tyr
NP_001394301.1:p.Asp208Tyr
NP_001394302.1:p.Asp208Tyr
NP_001394303.1:p.Asp208Tyr
NP_001394304.1:p.Asp208Tyr
NP_001394305.1:p.Asp208Tyr
NP_001394306.1:p.Asp208Tyr
NP_001394307.1:p.Asp208Tyr
NP_001394308.1:p.Asp208Tyr
NC_000003.11:g.15686045G>T
NM_001281723.3:c.622G>T
NM_001281725.2:c.622G>T
NM_001323582.1:c.622G>T
P43251:p.Asp228Tyr

Protein change:

D208Y

Links:

UniProtKB: P43251#VAR_005115; dbSNP: rs397514380

NCBI 1000 Genomes Browser:

rs397514380

Molecular consequence:

NM_001370753.1:c.399+2481G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000060.4:c.682G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370752.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.622G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407379.1:c.622G>T - 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
SCV004211405	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 17, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004373059	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9654207, 24797656, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004211405

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 17, 2024)

unknown

clinical testing

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

SCV004373059

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 8, 2023)

germline

clinical testing

PubMed (3)
[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

Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene.

Swango KL, Demirkol M, Hüner G, Pronicka E, Sykut-Cegielska J, Schulze A, Mayatepek E, Wolf B.

Hum Genet. 1998 May;102(5):571-5. Erratum in: Hum Genet 1998 Jun;102(6):712.

PubMed [citation]

PMID:: 9654207

See all PubMed Citations (4)

Details of each submission

From Baylor Genetics, SCV004211405.2

#	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, SCV004373059.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 228 of the BTD protein (p.Asp228Tyr). This variant is present in population databases (rs397514380, gnomAD 0.006%). This missense change has been observed in individual(s) with partial biotinidase deficiency (PMID: 9654207; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 25035). 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. This variant disrupts the p.Asp228 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 24797656; Invitae), which suggests that this may be a clinically significant amino acid residue. 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: Nov 24, 2024

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