NM_001199107.2(TBC1D24):c.724C>T (p.Arg242Cys) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 26, 2024
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:: RCV000651571.13

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.724C>T (p.Arg242Cys)]

NM_001199107.2(TBC1D24):c.724C>T (p.Arg242Cys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_001199107.2(TBC1D24):c.724C>T (p.Arg242Cys)

Other names:

p.R242C:CGC>TGC

HGVS:

NC_000016.10:g.2496872C>T
NG_028170.1:g.26727C>T
NM_001199107.1:c.[724C>T]
NM_001199107.2:c.724C>TMANE SELECT
NM_020705.3:c.724C>T
NP_001186036.1:p.Arg242Cys
NP_001186036.1:p.Arg242Cys
NP_065756.1:p.Arg242Cys
NC_000016.9:g.2546873C>T
NM_001199107.1:c.724C>T
NM_001199107.1:c.[724C>T]
NM_001199107.2:c.724C>T
NM_020705.2:c.724C>T
Q9ULP9:p.Arg242Cys

Protein change:

R242C; ARG242CYS

Links:

UniProtKB: Q9ULP9#VAR_070915; OMIM: 613577.0007; dbSNP: rs398122965

NCBI 1000 Genomes Browser:

rs398122965

Molecular consequence:

NM_001199107.2:c.724C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_020705.3:c.724C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000773425	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 26, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24291220, 31780880, 27281533, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000773425

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 26, 2024)

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

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

Rare Variants in 48 Genes Account for 42% of Cases of Epilepsy With or Without Neurodevelopmental Delay in 246 Pediatric Patients.

Fernández-Marmiesse A, Roca I, Díaz-Flores F, Cantarín V, Pérez-Poyato MS, Fontalba A, Laranjeira F, Quintans S, Moldovan O, Felgueroso B, Rodríguez-Pedreira M, Simón R, Camacho A, Quijada P, Ibanez-Mico S, Domingno MR, Benito C, Calvo R, Pérez-Cejas A, Carrasco ML, Ramos F, Couce ML, et al.

Front Neurosci. 2019;13:1135. doi: 10.3389/fnins.2019.01135.

PubMed [citation]

PMID:: 31780880
PMCID:: PMC6856296

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000773425.4

#	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 replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 242 of the TBC1D24 protein (p.Arg242Cys). This variant is present in population databases (rs398122965, gnomAD 0.007%). This missense change has been observed in individuals with autosomal recessive TBC1D24-related conditions (PMID: 24291220, 31780880). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 91395). 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 TBC1D24 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects TBC1D24 function (PMID: 27281533). 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: Oct 8, 2024

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