NM_001199107.2(TBC1D24):c.878G>A (p.Arg293His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 13, 2019
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:: RCV000826046.11

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.878G>A (p.Arg293His)]

NM_001199107.2(TBC1D24):c.878G>A (p.Arg293His)

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.878G>A (p.Arg293His)

Other names:

p.R293H:CGC>CAC; p.Arg293His

HGVS:

NC_000016.10:g.2497026G>A
NG_028170.1:g.26881G>A
NM_001199107.2:c.878G>AMANE SELECT
NM_020705.3:c.878G>A
NP_001186036.1:p.Arg293His
NP_065756.1:p.Arg293His
NC_000016.9:g.2547027G>A
NM_001199107.1:c.878G>A

Protein change:

R293H

Links:

dbSNP: rs199700840

NCBI 1000 Genomes Browser:

rs199700840

Molecular consequence:

NM_001199107.2:c.878G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020705.3:c.878G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000967538	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Feb 13, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24387994, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000967538

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Feb 13, 2019)

germline

clinical testing

PubMed (2)
[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	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in TBC1D24, a gene associated with epilepsy, also cause nonsyndromic deafness DFNB86.

Rehman AU, Santos-Cortez RL, Morell RJ, Drummond MC, Ito T, Lee K, Khan AA, Basra MA, Wasif N, Ayub M, Ali RA, Raza SI; University of Washington Center for Mendelian Genomics, Nickerson DA, Shendure J, Bamshad M, Riazuddin S, Billington N, Khan SN, Friedman PL, Griffith AJ, Ahmad W, et al.

Am J Hum Genet. 2014 Jan 2;94(1):144-52. doi: 10.1016/j.ajhg.2013.12.004.

PubMed [citation]

PMID:: 24387994
PMCID:: PMC3882911

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967538.2

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

Description

The p.Arg293His variant in TBC1D24 has not been previously reported in individuals with hearing loss or DOORS syndrome, but has been identified in 0.034% (43/128356) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 207519). A different missense variant at the same position (p.Arg293Pro) has been reported to segregate with hearing loss in a Pakistani family (Rehman 2014). Computational prediction tools and conservation analysis suggest that the p.Arg293His variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM5_Supporting, PM2_Supporting, PP3.

#	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		1	not provided	1	not provided

Last Updated: Apr 20, 2025

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