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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 28, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000470479.8

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]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 1 (DEE1)
Synonyms:: INFANTILE SPASM SYNDROME, X-LINKED 1; X-linked infantile spasms; West's syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010632; MedGen: C3463992; OMIM: 308350

Name:: Autosomal dominant nonsyndromic hearing loss 65
Synonyms:: Deafness, autosomal dominant 65
Identifiers:: MONDO: MONDO:0014470; MedGen: C3892048; Orphanet: 90635; OMIM: 616044

Name:: Caused by mutation in the TBC1 domain family, member 24
Identifiers:: MedGen: CN236805

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000549907	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23526554, 24291220, 25557349, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000549907

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 28, 2023)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel compound heterozygous mutations in TBC1D24 cause familial malignant migrating partial seizures of infancy.

Milh M, Falace A, Villeneuve N, Vanni N, Cacciagli P, Assereto S, Nabbout R, Benfenati F, Zara F, Chabrol B, Villard L, Fassio A.

Hum Mutat. 2013 Jun;34(6):869-72. doi: 10.1002/humu.22318. Epub 2013 Apr 12.

PubMed [citation]

PMID:: 23526554

The genetic basis of DOORS syndrome: an exome-sequencing study.

Campeau PM, Kasperaviciute D, Lu JT, Burrage LC, Kim C, Hori M, Powell BR, Stewart F, Félix TM, van den Ende J, Wisniewska M, Kayserili H, Rump P, Nampoothiri S, Aftimos S, Mey A, Nair LD, Begleiter ML, De Bie I, Meenakshi G, Murray ML, Repetto GM, et al.

Lancet Neurol. 2014 Jan;13(1):44-58. doi: 10.1016/S1474-4422(13)70265-5. Epub 2013 Nov 29.

PubMed [citation]

PMID:: 24291220
PMCID:: PMC3895324

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000549907.7

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

Description

This sequence change creates a premature translational stop signal (p.His336Glnfs*12) in the TBC1D24 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TBC1D24 are known to be pathogenic (PMID: 23526554, 24291220). This variant is present in population databases (rs398122967, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with autosomal recessive DOORS syndrome or with early-onset epileptic encephalopathy (PMID: 24291220, 25557349). ClinVar contains an entry for this variant (Variation ID: 91398). For these reasons, this variant has been classified as Pathogenic.

#	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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