Submissions for variant NM_001199107.2(TBC1D24):c.629C>T (p.Ala210Val)

gnomAD frequency: 0.00001  dbSNP: rs771442254

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001307263	SCV001496668	uncertain significance	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2020-08-02	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with valine at codon 210 of the TBC1D24 protein (p.Ala210Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs771442254, ExAC 0.01%). This variant has not been reported in the literature in individuals with TBC1D24-related conditions. 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 not expected to disrupt TBC1D24 protein function. 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.