NM_001199107.2(TBC1D24):c.1008del (p.His336fs) AND DOORS syndrome

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jun 7, 2019
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:: RCV000076916.20

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.1008del (p.His336fs)]

NM_001199107.2(TBC1D24):c.1008del (p.His336fs)

Gene:

TBC1D24:TBC1 domain family member 24 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_001199107.2(TBC1D24):c.1008del (p.His336fs)

HGVS:

NC_000016.10:g.2498262del
NG_028170.1:g.28117del
NM_001199107.2:c.1008delMANE SELECT
NM_020705.3:c.990del
NP_001186036.1:p.His336fs
NP_065756.1:p.His330fs
NC_000016.9:g.2548263del
NM_001199107.1:c.1008del
NM_001199107.1:c.1008delT
NM_001199107.2:c.1008delTMANE SELECT
NP_001186036.1:p.His336Glnfs*12
p.H336QfsX12

Protein change:

H330fs

Links:

OMIM: 613577.0010; dbSNP: rs398122967

NCBI 1000 Genomes Browser:

rs398122967

Molecular consequence:

NM_001199107.2:c.1008del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020705.3:c.990del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: DOORS syndrome (DOORS)
Synonyms:: DOOR SYNDROME; Deafness onychodystrophy osteodystrophy and mental retardation syndrome; DRC SYNDROME; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009079; MedGen: C0795934; Orphanet: 3231; Orphanet: 79500; OMIM: 220500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000108713	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000211969	Division of Medical Genetics; Sainte-Justine Hospital	no assertion criteria provided	Pathogenic (Dec 22, 2014)	germline	literature only	Citation Link,
SCV000266462	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	criteria provided, single submitter (Campeau et al. (Lancet Neurol 2014))	Pathogenic (Jan 1, 2014)	germline	research	PubMed (5) [See all records that cite these PMIDs] 25169651, 25719194, 23806086, 24088043, 24291220
SCV001150278	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Pathogenic (Jun 7, 2019)	maternal	clinical testing	Citation Link,
SCV002106362	GeneReviews	no classification provided	not provided	germline	literature only

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	2	not provided	not provided	not provided	literature only, research
not provided	germline	no	3	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	literature only
not provided	maternal	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

DOORS syndrome: phenotype, genotype and comparison with Coffin-Siris syndrome.

Campeau PM, Hennekam RC; DOORS syndrome collaborative group.

Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):327-32. doi: 10.1002/ajmg.c.31412. Epub 2014 Aug 28.

PubMed [citation]

PMID:: 25169651

TBC1D24-Related Disorders..

Balestrini S, Campeau PM, Mei D, Guerrini R, Sisodiya S.

2015 Feb 26 [updated 2024 Oct 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025.

PubMed [citation]

PMID:: 25719194

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000108713.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a German patient with deafness, onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome (DOORS; 220500), Campeau et al. (2014) identified compound heterozygosity for 2 mutations in the TBC1D24 gene: a 1-bp deletion (c.1008delT), resulting in a frameshift and premature termination (His336GlnfsTer12), and a splice site mutation in intron 5 (c.1206+5G-A; 613577.0011). The heterozygous c.1008delT mutation was found in 2 of 6,118 individuals in the Exome Variant Server. Fibroblasts from this patient showed 5% TBC1D24 mRNA and no detectable protein compared to controls, consistent with a loss of function. An unrelated French patient was heterozygous for the c.1008delT mutation, but a second mutation was not identified.

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

From Division of Medical Genetics; Sainte-Justine Hospital, SCV000211969.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

#	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 Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine, SCV000266462.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (5)
2	not provided	3	not provided	not provided	research	PubMed (5)

Description

We identified 26 families with DOORS syndrome; each patient had at least 3 of the 5 well-described features of DOORS syndrome, which include deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. A combination of whole-exome sequencing and Sanger sequencing identified homozygous or compound heterozygous pathogenic variants in TBC1D24 in 11 individuals from 9 families.

#	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		1	not provided	2	not provided
2	germline	no	not provided	not provided	not provided		3	not provided	not provided	not provided

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV001150278.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	maternal	yes	1	blood	not provided		1	not provided	not provided	not provided

From GeneReviews, SCV002106362.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	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: Apr 20, 2025

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