Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481616 | SCV000567838 | pathogenic | not provided | 2017-01-30 | criteria provided, single submitter | clinical testing | The Q20X pathogenic variant in the TBC1D24 gene has been reported previously (also reported incorrectly as Q20E), in the compound heterozygous state along with a missense variant, in two brothers with DOORS syndrome. Clinical features included developmental delay/intellectual disability, abnormal nails, abnormal fingers and toes, deafness, and seizures (Campeau et al., 2014; Balestrini et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q20X variant was not observed in approximately 6400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Q20X as a pathogenic variant. |
| Labcorp Genetics |
RCV001865442 | SCV002237397 | pathogenic | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2023-07-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 419782). This premature translational stop signal has been observed in individual(s) with clinical features of TBC1D24-related conditions (PMID: 27281533). This variant is present in population databases (rs201257588, gnomAD 0.03%). This sequence change creates a premature translational stop signal (p.Gln20*) in the TBC1D24 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TBC1D24 are known to be pathogenic (PMID: 23526554, 24291220). |