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NM_001199107.2(TBC1D24):c.116C>A (p.Ala39Glu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 8, 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:
RCV001223084.8

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.116C>A (p.Ala39Glu)]

NM_001199107.2(TBC1D24):c.116C>A (p.Ala39Glu)

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.116C>A (p.Ala39Glu)
Other names:
p.Ala39Glu
HGVS:
  • NC_000016.10:g.2496264C>A
  • NG_028170.1:g.26119C>A
  • NM_001199107.2:c.116C>AMANE SELECT
  • NM_020705.3:c.116C>A
  • NP_001186036.1:p.Ala39Glu
  • NP_065756.1:p.Ala39Glu
  • NC_000016.9:g.2546265C>A
  • NM_001199107.1:c.116C>A
Protein change:
A39E
Links:
dbSNP: rs773916549
NCBI 1000 Genomes Browser:
rs773916549
Molecular consequence:
  • NM_001199107.2:c.116C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020705.3:c.116C>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
SCV001395217Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 8, 2023) 		germlineclinical testing

PubMed (3)
[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

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

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
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001395217.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Ala39 amino acid residue in TBC1D24. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27281533, 31112829; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 449916). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is present in population databases (rs773916549, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 39 of the TBC1D24 protein (p.Ala39Glu).

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

Last Updated: Sep 29, 2024