Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000254691 | SCV007118794 | pathogenic | not provided | 2025-10-01 | criteria provided, single submitter | clinical testing | TBC1D24: PM3:Very Strong, PM2 |
| 3billion | RCV005868064 | SCV006584725 | pathogenic | Developmental and epileptic encephalopathy, 16 | 2025-03-28 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000254691 | SCV004238751 | likely pathogenic | not provided | 2024-07-10 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001330478 | SCV001522162 | pathogenic | DOORS syndrome | 2019-10-22 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Ambry Genetics | RCV000623272 | SCV000741949 | likely pathogenic | Inborn genetic diseases | 2021-07-13 | criteria provided, single submitter | clinical testing | The c.845C>G (p.P282R) alteration is located in exon 2 (coding exon 1) of the TBC1D24 gene. This alteration results from a C to G substitution at nucleotide position 845, causing the proline (P) at amino acid position 282 to be replaced by an arginine (R). Based on data from the Genome Aggregation Database (gnomAD), the TBC1D24 c.845C>G alteration was observed in 0.02% (46/280780) of total alleles studied, with a frequency of 0.13% (45/35374) in the Latino subpopulation. This variant has been reported in the compound heterozygous state in three individuals with epilepsy (Appavu, 2016; Balestrini, 2016; Hamdan, 2017). The in silico prediction for the p.P282R alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic. |
| Labcorp Genetics |
RCV006606330 | SCV000549904 | pathogenic | Developmental and epileptic encephalopathy, 1; not provided; Autosomal dominant nonsyndromic hearing loss 65 | 2025-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 282 of the TBC1D24 protein (p.Pro282Arg). This variant is present in population databases (rs747538224, gnomAD 0.1%). This missense change has been observed in individual(s) with autosomal recessive epileptic encephalopathy (PMID: 27502353, 29100083; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 207505). Invitae Evidence 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 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. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000254691 | SCV000243339 | pathogenic | not provided | 2025-10-02 | criteria provided, single submitter | clinical testing | Reported previously in individuals with clinical features consistent with TBC1D24-related DOORS spectrum disorder who also harbored a second TBC1D24 variant (PMID: 27502353, 27281533); 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: 27281533, 29100083, 33281559, 27502353, 34926809, 31440721) |
| Clinical Genomics Laboratory, |
RCV000254691 | SCV001427226 | pathogenic | not provided | 2020-03-02 | no assertion criteria provided | clinical testing | The p.Pro282Arg variant in the TBC1D24 gene has been previously reported in at least 17 unrelated individuals with seizures and developmental delay, and co-segregated with disease in at least 3 affected relatives from 3 families (Appavu et al., 2016; GeneDx, personal communication, March 2, 2020; Hamdan et al., 2017; Invitae, personal communication, February 12, 2020). All affected individuals were homozygous or compound heterozygous. This variant was determined to be in trans with at least 4 different likely pathogenic or pathogenic variants consistent with autosomal recessive inheritance (GeneDx, personal communication, March 2, 2020; Hamdan et al., 2017; Invitae, personal communication, February 12, 2020). The presence of this variant with a diseaseassociated variant on the opposite allele increases suspicion for its pathogenicity. The p.Pro282Arg variant has also been identified in 45/35,374 Latino chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Computational tools predict that this variant is deleterious; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Pro282Arg variant as pathogenic for autosomal recessive TBC1D24-associated disorders based on the information above. [ACMG evidence codes used: PM2; PM3_verystrong; PP1_moderate; PP3] |
| Clinical Molecular Genetics Laboratory, |
RCV000678853 | SCV000805044 | uncertain significance | developmental delay with seizures | 2016-08-15 | flagged submission | clinical testing | |
| Genetic Services Laboratory, |
RCV000189692 | SCV000249121 | uncertain significance | not specified | 2014-08-08 | flagged submission | clinical testing |