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

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 12, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV001578266.7

Allele description [Variation Report for NM_001370658.1(BTD):c.1301A>G (p.Tyr434Cys)]

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:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001805821	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 12, 2021)	germline	clinical testing	Citation Link,
SCV002047169	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely pathogenic (May 28, 2021)	unknown	clinical testing	PubMed (8) [See all records that cite these PMIDs] 26810761, 15776412, 31973013, 30616616, 33312878, 29995633, 29353266, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001805821

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 12, 2021)

germline

clinical testing

Citation Link,

SCV002047169

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely pathogenic
(May 28, 2021)

unknown

clinical testing

PubMed (8)
[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	germline	yes	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

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

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 GeneDx, SCV001805821.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Reported in one individual with profound biotinidase deficiency in whom two known pathogenic variants in the BTD gene were also found. In this individual, the Y454C variant was in cis with one of the known pathogenic variants with the other pathogenic variant on the opposite allele (Wolf et al., 2005); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect This variant is associated with the following publications: (PMID: 30616616, 26810761, 15776412, 31973013)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002047169.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

The variant has been reported in multiple individuals with profound or partial biotinidase deficiency (PMID: 33312878 (2020), 29995633 (2018), 26810761 (2016), 15776412 (2005)). Variant occurs in 3 or more cases with a lone recessive pathogenic/likely pathogenic variant in the same gene, and at least 3 cases have phenotype known to be consistent with disease. Variant is predicted to have a damaging effect on the protein.Based on the available information, the variant is predicted to be likely pathogenic.

#	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 20, 2024

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