ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs199744635
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000823886 SCV000964757 pathogenic Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2022-08-23 criteria provided, single submitter clinical testing 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.

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