NM_001370658.1(BTD):c.1301A>G (p.Tyr434Cys) AND not specified

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 29, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002282207.3

Allele description

NM_001370658.1(BTD):c.1301A>G (p.Tyr434Cys)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.1301A>G (p.Tyr434Cys)

HGVS:

NC_000003.12:g.15645217A>G
NG_008019.2:g.48866A>G
NG_008019.3:g.48867A>G
NM_000060.4:c.1361A>G
NM_001281723.4:c.1301A>G
NM_001281724.3:c.1301A>G
NM_001281725.3:c.1301A>G
NM_001323582.2:c.1301A>G
NM_001370658.1:c.1301A>GMANE SELECT
NM_001370752.1:c.1015+286A>G
NM_001370753.1:c.399+3160A>G
NM_001407364.1:c.1301A>G
NM_001407365.1:c.1301A>G
NM_001407366.1:c.1301A>G
NM_001407367.1:c.1301A>G
NM_001407368.1:c.1301A>G
NM_001407369.1:c.1301A>G
NM_001407370.1:c.1301A>G
NM_001407371.1:c.1301A>G
NM_001407372.1:c.1301A>G
NM_001407373.1:c.1301A>G
NM_001407374.1:c.1301A>G
NM_001407375.1:c.1301A>G
NM_001407376.1:c.1301A>G
NM_001407377.1:c.1301A>G
NM_001407378.1:c.1301A>G
NP_000051.1:p.Tyr454Cys
NP_001268652.2:p.Tyr434Cys
NP_001268652.2:p.Tyr434Cys
NP_001268653.2:p.Tyr434Cys
NP_001268654.1:p.Tyr434Cys
NP_001268654.1:p.Tyr434Cys
NP_001310511.1:p.Tyr434Cys
NP_001310511.1:p.Tyr434Cys
NP_001357587.1:p.Tyr434Cys
NP_001394293.1:p.Tyr434Cys
NP_001394294.1:p.Tyr434Cys
NP_001394295.1:p.Tyr434Cys
NP_001394296.1:p.Tyr434Cys
NP_001394297.1:p.Tyr434Cys
NP_001394298.1:p.Tyr434Cys
NP_001394299.1:p.Tyr434Cys
NP_001394300.1:p.Tyr434Cys
NP_001394301.1:p.Tyr434Cys
NP_001394302.1:p.Tyr434Cys
NP_001394303.1:p.Tyr434Cys
NP_001394304.1:p.Tyr434Cys
NP_001394305.1:p.Tyr434Cys
NP_001394306.1:p.Tyr434Cys
NP_001394307.1:p.Tyr434Cys
NC_000003.11:g.15686724A>G
NM_000060.4:c.1361A>G
NM_001281723.3:c.1301A>G
NM_001281725.2:c.1301A>G
NM_001323582.1:c.1301A>G
NM_001370658.1:c.1301A>G

Protein change:

Y434C

Links:

dbSNP: rs397514345

NCBI 1000 Genomes Browser:

rs397514345

Molecular consequence:

NM_001370752.1:c.1015+286A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001370753.1:c.399+3160A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000060.4:c.1361A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002572127	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 29, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26810761, 29353266, 33189081, 34448386, 15776412 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002572127

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 29, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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

Citations

PubMed

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

Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey.

Seker Yilmaz B, Mungan NO, Kor D, Bulut D, Seydaoglu G, Öktem M, Ceylaner S.

J Pediatr Endocrinol Metab. 2018 Mar 28;31(3):339-343. doi: 10.1515/jpem-2017-0406.

PubMed [citation]

PMID:: 29353266

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002572127.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: BTD c.1301A>G (p.Tyr434Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00026 in 251422 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in BTD causing Biotinidase Deficiency (0.00026 vs 0.0046), allowing no conclusion about variant significance. c.1301A>G has been reported in the literature in newborns with features of biotinidase deficiency to include cases where it was reported in cis with another presumably pathogenic variant (example, Akgun_2021, Seker-Yilmaz_2018, Ercan_2020, Procter_2016, Wolf_2005). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function in a homozygous genotype (Ercan_2020). The most pronounced variant effect results in 26%-36% of normal activity depending upon the methodology used. The following publications have been ascertained in the context of this evaluation (PMID: 26810761, 29353266, 33189081, 34448386, 15776412). ClinVar contains an entry for this variant (Variation ID: 458806). Based on the evidence outlined above, the variant was classified as VUS-possibly 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: Jun 8, 2025

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