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NM_001199107.2(TBC1D24):c.679C>T (p.Arg227Trp) AND Inborn genetic diseases

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 30, 2021
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:
RCV002367670.2

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.679C>T (p.Arg227Trp)]

NM_001199107.2(TBC1D24):c.679C>T (p.Arg227Trp)

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.679C>T (p.Arg227Trp)
HGVS:
  • NC_000016.10:g.2496827C>T
  • NG_028170.1:g.26682C>T
  • NM_001199107.2:c.679C>TMANE SELECT
  • NM_020705.3:c.679C>T
  • NP_001186036.1:p.Arg227Trp
  • NP_065756.1:p.Arg227Trp
  • NC_000016.9:g.2546828C>T
  • NM_001199107.1:c.679C>T
Protein change:
R227W
Links:
dbSNP: rs748302886
NCBI 1000 Genomes Browser:
rs748302886
Molecular consequence:
  • NM_001199107.2:c.679C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020705.3:c.679C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002666286Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jul 30, 2021) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features.

Balestrini S, Milh M, Castiglioni C, Lüthy K, Finelli MJ, Verstreken P, Cardon A, Stražišar BG, Holder JL Jr, Lesca G, Mancardi MM, Poulat AL, Repetto GM, Banka S, Bilo L, Birkeland LE, Bosch F, Brockmann K, Cross JH, Doummar D, Félix TM, Giuliano F, et al.

Neurology. 2016 Jul 5;87(1):77-85. doi: 10.1212/WNL.0000000000002807. Epub 2016 Jun 8.

PubMed [citation]
PMID:
27281533
PMCID:
PMC4932231

Skywalker-TBC1D24 has a lipid-binding pocket mutated in epilepsy and required for synaptic function.

Fischer B, Lüthy K, Paesmans J, De Koninck C, Maes I, Swerts J, Kuenen S, Uytterhoeven V, Verstreken P, Versées W.

Nat Struct Mol Biol. 2016 Nov;23(11):965-973. doi: 10.1038/nsmb.3297. Epub 2016 Sep 26.

PubMed [citation]
PMID:
27669036
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002666286.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.679C>T (p.R227W) alteration is located in exon 2 (coding exon 1) of the TBC1D24 gene. This alteration results from a C to T substitution at nucleotide position 679, causing the arginine (R) at amino acid position 227 to be replaced by a tryptophan (W). Based on data from the Genome Aggregation Database (gnomAD) database, the TBC1D24 c.679C>T alteration was observed in <0.01% (3/249280) of total alleles studied, with a frequency of <0.01% (1/30602) in the South Asian subpopulation. This variant was identified in an individual with multifocal epilepsy in conjunction with p.A515V; however, the phase was not provided (Balestrini, 2016). It was also identified in conjunction with p.P135L in at least one Chinese individual with epilepsy (Zhang, 2019; Zhang, 2021). Based on internal structural analysis, this variant is more disruptive than known pathogenic variants (Fischer, 2016). The in silico prediction for the p.R227W alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic.

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

Last Updated: Sep 29, 2024