Submissions for variant NM_001199107.2(TBC1D24):c.734T>C (p.Leu245Pro)

gnomAD frequency: 0.00001  dbSNP: rs370477379

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768328	SCV000899008	uncertain significance	DOORS syndrome; Familial infantile myoclonic epilepsy; Autosomal recessive nonsyndromic hearing loss 86; Developmental and epileptic encephalopathy, 16; Autosomal dominant nonsyndromic hearing loss 65	2017-10-23	criteria provided, single submitter	clinical testing	TBC1D24 NM_001199107.1 exon 2 p.Leu245Pro (c.734T>C): This variant has not been reported in the literature but is present in 2/111650 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs370477379). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV000996171	SCV001150743	uncertain significance	not provided	2016-04-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001339150	SCV001532871	uncertain significance	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2025-01-12	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 245 of the TBC1D24 protein (p.Leu245Pro). This variant is present in population databases (rs370477379, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of TBC1D24-related conditions (PMID: 33229591). ClinVar contains an entry for this variant (Variation ID: 626176). 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) indicates that this missense variant is expected to disrupt TBC1D24 protein function with a positive predictive value of 95%. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224455	SCV003920528	uncertain significance	Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer's cramp syndrome; DOORS syndrome; Familial infantile myoclonic epilepsy; Autosomal recessive nonsyndromic hearing loss 86; Developmental and epileptic encephalopathy, 16; Autosomal dominant nonsyndromic hearing loss 65	2021-03-30	criteria provided, single submitter	clinical testing	TBC1D24 NM_001199107 exon 2 p.Leu245Pro (c.734T>C): This variant has not been reported in the literature but is present in 2/111650 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs370477379). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Athena Diagnostics	RCV000996171	SCV004229319	uncertain significance	not provided	2022-12-09	criteria provided, single submitter	clinical testing	Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Computational tools predict that this variant is damaging.