ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.115G>C (p.Ala39Pro)

dbSNP: rs770363653
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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 RCV001377313 SCV001574618 pathogenic Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2023-02-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 39 of the TBC1D24 protein (p.Ala39Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive TBC1D24-related conditions (PMID: 27281533; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1066340). 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.Ala39 amino acid residue in TBC1D24. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28292732, 30180405; Invitae). 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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