NM_001370658.1(BTD):c.992del (p.Thr331fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 13, 2020
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:: RCV000269677.4

Allele description [Variation Report for NM_001370658.1(BTD):c.992del (p.Thr331fs)]

NM_001370658.1(BTD):c.992del (p.Thr331fs)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.992del (p.Thr331fs)

HGVS:

NC_000003.12:g.15644908del
NG_008019.3:g.48558del
NM_000060.2:c.1052del
NM_001281723.4:c.992del
NM_001281724.3:c.992del
NM_001281725.3:c.992del
NM_001281726.2:c.*2770delC
NM_001323582.2:c.992del
NM_001370658.1:c.992delMANE SELECT
NM_001370752.1:c.992del
NM_001370753.1:c.399+2851del
NM_001407364.1:c.992del
NM_001407365.1:c.992del
NM_001407366.1:c.992del
NM_001407367.1:c.992del
NM_001407368.1:c.992del
NM_001407369.1:c.992del
NM_001407370.1:c.992del
NM_001407371.1:c.992del
NM_001407372.1:c.992del
NM_001407373.1:c.992del
NM_001407374.1:c.992del
NM_001407375.1:c.992del
NM_001407376.1:c.992del
NM_001407377.1:c.992del
NM_001407378.1:c.992del
NM_001407379.1:c.992del
NM_001407380.1:c.399+2851del
NM_001407398.1:c.399+2851del
NM_001407399.1:c.399+2851del
NM_001407400.1:c.399+2851del
NM_001407401.1:c.399+2851del
NP_001268652.2:p.Thr331fs
NP_001268653.2:p.Thr331fs
NP_001268654.1:p.Thr331fs
NP_001310511.1:p.Thr331fs
NP_001357587.1:p.Thr331fs
NP_001357681.1:p.Thr331fs
NP_001394293.1:p.Thr331fs
NP_001394294.1:p.Thr331fs
NP_001394295.1:p.Thr331fs
NP_001394296.1:p.Thr331fs
NP_001394297.1:p.Thr331fs
NP_001394298.1:p.Thr331fs
NP_001394299.1:p.Thr331fs
NP_001394300.1:p.Thr331fs
NP_001394301.1:p.Thr331fs
NP_001394302.1:p.Thr331fs
NP_001394303.1:p.Thr331fs
NP_001394304.1:p.Thr331fs
NP_001394305.1:p.Thr331fs
NP_001394306.1:p.Thr331fs
NP_001394307.1:p.Thr331fs
NP_001394308.1:p.Thr331fs
NC_000003.11:g.15686415del
NG_008019.2:g.48557del
NM_000060.2:c.1052delC
NM_000060.4:c.1052del
p.Thr351Lysfs*12

Protein change:

T331fs

Links:

dbSNP: rs397514398

NCBI 1000 Genomes Browser:

rs397514398

Molecular consequence:

NM_001281723.4:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281724.3:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281725.3:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001323582.2:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370658.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370752.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407364.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407365.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407366.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407367.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407368.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407369.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407370.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407371.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407372.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407373.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407374.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407375.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407376.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407377.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407378.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407379.1:c.992del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370753.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407380.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407398.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407399.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407400.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407401.1:c.399+2851del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329855	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Sep 27, 2018)	germline	clinical testing	Citation Link,
SCV000600935	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Nov 13, 2020)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12359137, 15776412, 20083419, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329855

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Sep 27, 2018)

germline

clinical testing

Citation Link,

SCV000600935

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Nov 13, 2020)

unknown

clinical testing

PubMed (4)
[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

Seventeen novel mutations that cause profound biotinidase deficiency.

Wolf B, Jensen K, Hüner G, Demirkol M, Baykal T, Divry P, Rolland MO, Perez-Cerdá C, Ugarte M, Straussberg R, Basel-Vanagaite L, Baumgartner ER, Suormala T, Scholl S, Das AM, Schweitzer S, Pronicka E, Sykut-Cegielska J.

Mol Genet Metab. 2002 Sep-Oct;77(1-2):108-11.

PubMed [citation]

PMID:: 12359137

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 (4)

Details of each submission

From GeneDx, SCV000329855.6

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

Description

The c.1052delC variant in the BTD gene has been reported previously in association with biotinidase deficiency (Wolf et al. 2002; Iqbal et al. 2010; Gannavarapu et al. 2015). The c.1052delC variant has been reported to be associated with profound biotinidase deficiency in a patient who also harbored a second frameshift variant as well as in a patient homozygous for c.1052delC (Wolf et al. 2002; Iqbal et al. 2010). However, a second patient homozygous for c.1052delC was reported with partial biotinidase deficiency (Iqbal et al. 2010). The c.1052delC deletion causes a frameshift starting with codon Threonine 351, changes this amino acid to a Lysine residue and creates a premature Stop codon at position 12 of the new reading frame, denoted p.Thr351LysfsX12. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation. The c.1052delC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, we interpret c.1052delC to be a pathogenic variant.

#	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, SCV000600935.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine