NM_001370658.1(BTD):c.1177G>A (p.Gly393Ser) AND Biotinidase deficiency

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Dec 5, 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:: RCV000032020.9

Allele description [Variation Report for NM_001370658.1(BTD):c.1177G>A (p.Gly393Ser)]

NM_001370658.1(BTD):c.1177G>A (p.Gly393Ser)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.1177G>A (p.Gly393Ser)

Other names:

G413S; p.Gly413Ser

HGVS:

NC_000003.12:g.15645093G>A
NG_008019.2:g.48742G>A
NG_008019.3:g.48743G>A
NM_000060.4:c.1237G>A
NM_001281723.4:c.1177G>A
NM_001281724.3:c.1177G>A
NM_001281725.3:c.1177G>A
NM_001323582.2:c.1177G>A
NM_001370658.1:c.1177G>AMANE SELECT
NM_001370752.1:c.1015+162G>A
NM_001370753.1:c.399+3036G>A
NM_001407364.1:c.1177G>A
NM_001407365.1:c.1177G>A
NM_001407366.1:c.1177G>A
NM_001407367.1:c.1177G>A
NM_001407368.1:c.1177G>A
NM_001407369.1:c.1177G>A
NM_001407370.1:c.1177G>A
NM_001407371.1:c.1177G>A
NM_001407372.1:c.1177G>A
NM_001407373.1:c.1177G>A
NM_001407374.1:c.1177G>A
NM_001407375.1:c.1177G>A
NM_001407376.1:c.1177G>A
NM_001407377.1:c.1177G>A
NM_001407378.1:c.1177G>A
NP_000051.1:p.Gly413Ser
NP_001268652.2:p.Gly393Ser
NP_001268652.2:p.Gly393Ser
NP_001268653.2:p.Gly393Ser
NP_001268654.1:p.Gly393Ser
NP_001268654.1:p.Gly393Ser
NP_001310511.1:p.Gly393Ser
NP_001310511.1:p.Gly393Ser
NP_001357587.1:p.Gly393Ser
NP_001394293.1:p.Gly393Ser
NP_001394294.1:p.Gly393Ser
NP_001394295.1:p.Gly393Ser
NP_001394296.1:p.Gly393Ser
NP_001394297.1:p.Gly393Ser
NP_001394298.1:p.Gly393Ser
NP_001394299.1:p.Gly393Ser
NP_001394300.1:p.Gly393Ser
NP_001394301.1:p.Gly393Ser
NP_001394302.1:p.Gly393Ser
NP_001394303.1:p.Gly393Ser
NP_001394304.1:p.Gly393Ser
NP_001394305.1:p.Gly393Ser
NP_001394306.1:p.Gly393Ser
NP_001394307.1:p.Gly393Ser
NC_000003.11:g.15686600G>A
NM_001281723.3:c.1177G>A
NM_001281725.2:c.1177G>A
NM_001323582.1:c.1177G>A

Protein change:

G393S

Links:

dbSNP: rs374141881

NCBI 1000 Genomes Browser:

rs374141881

Molecular consequence:

NM_001370752.1:c.1015+162G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001370753.1:c.399+3036G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000060.4:c.1237G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.1177G>A - 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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KRTAP4-12 keratin associated protein 4-12 [Homo sapiens]
KRTAP4-12 keratin associated protein 4-12 [Homo sapiens]
Gene ID:83755

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000630321	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 5, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25144890, 28492532
SCV000800639	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Dec 14, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001461223	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 16, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000630321

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 5, 2023)

germline

clinical testing

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

SCV000800639

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Dec 14, 2017)

unknown

clinical testing

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

Citation Link,

SCV001461223

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 16, 2020)

germline

clinical testing

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Outcomes of individuals with profound and partial biotinidase deficiency ascertained by newborn screening in Michigan over 25 years.

Jay AM, Conway RL, Feldman GL, Nahhas F, Spencer L, Wolf B.

Genet Med. 2015 Mar;17(3):205-9. doi: 10.1038/gim.2014.104. Epub 2014 Aug 21.

PubMed [citation]

PMID:: 25144890

Details of each submission

From Invitae, SCV000630321.4

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 413 of the BTD protein (p.Gly413Ser). This variant is present in population databases (rs374141881, gnomAD 0.003%). This missense change has been observed in individual(s) with partial biotinidase deficiency (PMID: 25144890). ClinVar contains an entry for this variant (Variation ID: 38577). 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 with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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

From Counsyl, SCV000800639.1

#	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

From Natera, Inc., SCV001461223.1

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

#	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: Feb 28, 2024

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