ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.503T>C (p.Leu168Pro)

gnomAD frequency: 0.00001  dbSNP: rs770847294
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001321656 SCV001512493 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2023-04-28 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TBC1D24 protein function. ClinVar contains an entry for this variant (Variation ID: 1021834). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is present in population databases (rs770847294, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 168 of the TBC1D24 protein (p.Leu168Pro).
GeneDx RCV004727135 SCV005331575 uncertain significance not provided 2023-08-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27694994)
Ambry Genetics RCV004968031 SCV005516183 uncertain significance Inborn genetic diseases 2024-08-28 criteria provided, single submitter clinical testing The c.503T>C (p.L168P) alteration is located in exon 2 (coding exon 1) of the TBC1D24 gene. This alteration results from a T to C substitution at nucleotide position 503, causing the leucine (L) at amino acid position 168 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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