NM_001370658.1(BTD):c.185C>T (p.Ala62Val) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 14, 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:: RCV001800312.5

Allele description [Variation Report for NM_001370658.1(BTD):c.185C>T (p.Ala62Val)]

NM_001370658.1(BTD):c.185C>T (p.Ala62Val)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.185C>T (p.Ala62Val)

HGVS:

NC_000003.12:g.15635624C>T
NG_008019.2:g.39273C>T
NM_000060.4:c.245C>T
NM_001281723.4:c.185C>T
NM_001281724.3:c.185C>T
NM_001281725.3:c.185C>T
NM_001281726.3:c.185C>T
NM_001323582.2:c.185C>T
NM_001370658.1:c.185C>TMANE SELECT
NM_001370752.1:c.185C>T
NM_001370753.1:c.185C>T
NM_001407364.1:c.185C>T
NM_001407365.1:c.185C>T
NM_001407366.1:c.185C>T
NM_001407367.1:c.185C>T
NM_001407368.1:c.185C>T
NM_001407369.1:c.185C>T
NM_001407370.1:c.185C>T
NM_001407371.1:c.185C>T
NM_001407372.1:c.185C>T
NM_001407373.1:c.185C>T
NM_001407374.1:c.185C>T
NM_001407375.1:c.185C>T
NM_001407376.1:c.185C>T
NM_001407377.1:c.185C>T
NM_001407378.1:c.185C>T
NM_001407379.1:c.185C>T
NM_001407380.1:c.185C>T
NM_001407381.1:c.185C>T
NM_001407382.1:c.185C>T
NM_001407383.1:c.185C>T
NM_001407384.1:c.185C>T
NM_001407386.1:c.185C>T
NM_001407388.1:c.185C>T
NM_001407390.1:c.185C>T
NM_001407392.1:c.185C>T
NM_001407394.1:c.185C>T
NM_001407395.1:c.185C>T
NM_001407396.1:c.185C>T
NM_001407397.1:c.185C>T
NM_001407398.1:c.185C>T
NM_001407399.1:c.185C>T
NM_001407400.1:c.185C>T
NM_001407401.1:c.185C>T
NP_000051.1:p.Ala82Val
NP_001268652.2:p.Ala62Val
NP_001268652.2:p.Ala62Val
NP_001268653.2:p.Ala62Val
NP_001268654.1:p.Ala62Val
NP_001268654.1:p.Ala62Val
NP_001268655.2:p.Ala62Val
NP_001268655.2:p.Ala62Val
NP_001310511.1:p.Ala62Val
NP_001310511.1:p.Ala62Val
NP_001357587.1:p.Ala62Val
NP_001357681.1:p.Ala62Val
NP_001357682.1:p.Ala62Val
NP_001394293.1:p.Ala62Val
NP_001394294.1:p.Ala62Val
NP_001394295.1:p.Ala62Val
NP_001394296.1:p.Ala62Val
NP_001394297.1:p.Ala62Val
NP_001394298.1:p.Ala62Val
NP_001394299.1:p.Ala62Val
NP_001394300.1:p.Ala62Val
NP_001394301.1:p.Ala62Val
NP_001394302.1:p.Ala62Val
NP_001394303.1:p.Ala62Val
NP_001394304.1:p.Ala62Val
NP_001394305.1:p.Ala62Val
NP_001394306.1:p.Ala62Val
NP_001394307.1:p.Ala62Val
NP_001394308.1:p.Ala62Val
NP_001394309.1:p.Ala62Val
NP_001394310.1:p.Ala62Val
NP_001394311.1:p.Ala62Val
NP_001394312.1:p.Ala62Val
NP_001394313.1:p.Ala62Val
NP_001394315.1:p.Ala62Val
NP_001394317.1:p.Ala62Val
NP_001394319.1:p.Ala62Val
NP_001394321.1:p.Ala62Val
NP_001394323.1:p.Ala62Val
NP_001394324.1:p.Ala62Val
NP_001394325.1:p.Ala62Val
NP_001394326.1:p.Ala62Val
NP_001394327.1:p.Ala62Val
NP_001394328.1:p.Ala62Val
NP_001394329.1:p.Ala62Val
NP_001394330.1:p.Ala62Val
NC_000003.11:g.15677131C>T
NM_001281723.3:c.185C>T
NM_001281725.2:c.185C>T
NM_001281726.2:c.185C>T
NM_001323582.1:c.185C>T
NM_001370658.1:c.185C>T

Protein change:

A62V

Links:

dbSNP: rs397507171

NCBI 1000 Genomes Browser:

rs397507171

Molecular consequence:

NM_000060.4:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281726.3:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370752.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370753.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407379.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407380.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407381.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407382.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407383.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407384.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407386.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407388.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407390.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407392.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407394.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407395.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407396.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407397.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407398.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407399.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407400.1:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407401.1:c.185C>T - 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
SCV002047133	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (May 20, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26810761, 26467025
SCV005040295	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 14, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002047133

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(May 20, 2021)

unknown

clinical testing

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

SCV005040295

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 14, 2024)

germline

clinical testing

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

Citation Link

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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

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

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002047133.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005040295.2

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

Description

Variant summary: BTD c.185C>T (p.Ala62Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251408 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.185C>T has been reported in the literature at a compound heterozygous state along with a pathogenic missense in at-least one individual affected with Biotinidase Deficiency (example, Procter_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Additionally, at least two variants at the Ala62 residue have been reported as DM in HGMD (p.A62D and p.A62G), suggesting that this codon might be functionally important. However, further evidence is needed to validate the pathogenicity of those two variants. The following publication have been ascertained in the context of this evaluation (PMID: 26810761). ClinVar contains an entry for this variant (Variation ID: 24989). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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 20, 2024

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