Submissions for variant NM_001199107.2(TBC1D24):c.752del (p.Phe251fs)

dbSNP: rs766769998

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001951260	SCV002243130	pathogenic	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2023-05-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe251Serfs*4) 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). This variant is present in population databases (rs766769998, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. ClinVar contains an entry for this variant (Variation ID: 1456664). For these reasons, this variant has been classified as Pathogenic.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV004785414	SCV005399195	pathogenic	Autosomal recessive nonsyndromic hearing loss 86	2020-06-11	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene (PMID: 27281533). (N) 0108 - This gene is known to be associated with both recessive and dominant disease. Only a single missense has been reported to cause autosomal dominant disease (OMIM). (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 2 of 8). (P) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (3 heterozygotes, 0 homozygotes). (P) 0701 - Comparable variants also predicted to result in an NMD predicted variant, have very strong previous evidence for pathogenicity in patients with epileptic encephalopathy and familial myoclonic epilepsy, and less commonly recessive deafness (Decipher, PMID: 27281533. PMID: 26371875, OMIM). (P) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
GenomeConnect - Brain Gene Registry	RCV003987944	SCV004804544	not provided	DOORS syndrome; Familial infantile myoclonic epilepsy; Autosomal recessive nonsyndromic hearing loss 86; Developmental and epileptic encephalopathy, 16; Autosomal dominant nonsyndromic hearing loss 65		no assertion provided	phenotyping only	Variant classified as Pathogenic and reported on 11-10-2022 by Invitae . Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.