Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000540418 | SCV000654198 | pathogenic | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 515 of the TBC1D24 protein (p.Ala515Val). This variant is present in population databases (rs267607105, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of autosomal recessive TBC1D24-related conditions (PMID: 20727515, 27281533, 31112829; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.Ala509Val. ClinVar contains an entry for this variant (Variation ID: 49). 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 with a positive predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TBC1D24 function (PMID: 20727515, 26668325). For these reasons, this variant has been classified as Pathogenic. |
| Eurofins Ntd Llc |
RCV000730513 | SCV000858255 | uncertain significance | not provided | 2017-11-17 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000730513 | SCV001371120 | pathogenic | not provided | 2024-03-01 | criteria provided, single submitter | clinical testing | TBC1D24: PM3:Very Strong, PM2, PS3:Supporting |
| Mendelics | RCV002247226 | SCV002517440 | likely pathogenic | DOORS syndrome | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000730513 | SCV002552654 | likely pathogenic | not provided | 2022-07-12 | criteria provided, single submitter | clinical testing | Published functional studies showed that this variant had significantly higher levels of protein S-nitrosylation and impaired neurite growth and length (Finelli et al., 2016; Falace et al., 2010); 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: 25719194, 24387994, 34341188, 32663648, 31257402, 28761347, 26668325, 24729539, 28428906, 24291220, 34811399, 30180405, 35350397, 27281533, 31112829, 20727515) |
| Ambry Genetics | RCV002399304 | SCV002707381 | likely pathogenic | Inborn genetic diseases | 2019-04-22 | criteria provided, single submitter | clinical testing | The p.A515V variant (also known as c.1544C>T), located in coding exon 7 of the TBC1D24 gene, results from a C to T substitution at nucleotide position 1544. The alanine at codon 515 is replaced by valine, an amino acid with similar properties. This variant was identified in 7 relatives with familial infantile myoclonic epilepsy in trans with p.D147H (Balestrini S et al. Neurology, 2016 Jul;87:77-85). It was also identified in an individual with early-onset epileptic encephalopathy in conjunction with p.P93S and in an individual with multifocal epilepsy in conjunction with p.R227W; however, the phase was not provided (Falace A et al. Am. J. Hum. Genet., 2010 Sep;87:365-70). This amino acid position is highly conserved in available vertebrate species. Based on data from gnomAD, the T allele has an overall frequency of approximately <0.01% (4/271284). In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| OMIM | RCV000000066 | SCV000020209 | pathogenic | Familial infantile myoclonic epilepsy | 2010-09-10 | no assertion criteria provided | literature only | |
| Division of Medical Genetics; Sainte- |
RCV000000066 | SCV000211972 | pathogenic | Familial infantile myoclonic epilepsy | 2014-12-22 | no assertion criteria provided | literature only |