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NM_001199107.2(TBC1D24):c.725G>A (p.Arg242His) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 23, 2022
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:
RCV000823886.6

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.725G>A (p.Arg242His)]

NM_001199107.2(TBC1D24):c.725G>A (p.Arg242His)

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.725G>A (p.Arg242His)
HGVS:
  • NC_000016.10:g.2496873G>A
  • NG_028170.1:g.26728G>A
  • NM_001199107.2:c.725G>AMANE SELECT
  • NM_020705.3:c.725G>A
  • NP_001186036.1:p.Arg242His
  • NP_065756.1:p.Arg242His
  • NC_000016.9:g.2546874G>A
  • NM_001199107.1:c.725G>A
Protein change:
R242H
Links:
dbSNP: rs199744635
NCBI 1000 Genomes Browser:
rs199744635
Molecular consequence:
  • NM_001199107.2:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020705.3:c.725G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000964757Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 23, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Infantile epilepsy with multifocal myoclonus caused by TBC1D24 mutations.

Zhang J, Chen J, Zeng Q, Zhang L, Tian X, Yang X, Yang Z, Wu Y, Wu X, Zhang Y.

Seizure. 2019 Jul;69:228-234. doi: 10.1016/j.seizure.2019.05.010. Epub 2019 May 13.

PubMed [citation]
PMID:
31112829

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000964757.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 242 of the TBC1D24 protein (p.Arg242His). This variant is present in population databases (rs199744635, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recesesive TBC1D24-related conditions (PMID: 31112829). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 665574). 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. This variant disrupts the p.Arg242 amino acid residue in TBC1D24. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24291220, 27281533, 31780880). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024