Submissions for variant NM_001199107.2(TBC1D24):c.866C>T (p.Ala289Val)

gnomAD frequency: 0.00001  dbSNP: rs748759187

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000501813	SCV000597399	likely pathogenic	Familial infantile myoclonic epilepsy	2015-12-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001857175	SCV002265128	uncertain significance	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2023-07-07	criteria provided, single submitter	clinical testing	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. 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: 436948). This missense change has been observed in individual(s) with autosomal recessive TBD1D24-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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 289 of the TBC1D24 protein (p.Ala289Val).
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV001824142	SCV002073947	likely pathogenic	Developmental and epileptic encephalopathy, 16	2022-02-08	no assertion criteria provided	clinical testing