ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.1384G>A (p.Glu462Lys)

gnomAD frequency: 0.00004  dbSNP: rs368678094
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001226467 SCV001398781 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2023-04-23 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 not expected to disrupt TBC1D24 protein function. ClinVar contains an entry for this variant (Variation ID: 954076). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is present in population databases (rs368678094, gnomAD 0.04%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 462 of the TBC1D24 protein (p.Glu462Lys).
GeneDx RCV001552116 SCV001772758 uncertain significance not provided 2021-04-26 criteria provided, single submitter clinical testing Reported as a known variant in a study of individuals with DOORS syndrome; however no additional information was provided (Campeau et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24291220)
PreventionGenetics, part of Exact Sciences RCV003405412 SCV004109473 uncertain significance TBC1D24-related condition 2023-07-12 criteria provided, single submitter clinical testing The TBC1D24 c.1384G>A variant is predicted to result in the amino acid substitution p.Glu462Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.050% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2550350-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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