Submissions for variant NM_001199107.2(TBC1D24):c.229ATCGTGGGCAAG[1] (p.77IVGK[1])

dbSNP: rs761918906

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478982	SCV000565942	pathogenic	not provided	2023-07-15	criteria provided, single submitter	clinical testing	In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion of 4 amino acids in a non-repeat region; This variant is associated with the following publications: (PMID: 32663648, 31112829, 29416524, 29429257, 30180405, 31257402, 31216804, 33333793, 34120799, 35413638)
Ambry Genetics	RCV002311804	SCV000847152	uncertain significance	Inborn genetic diseases	2016-08-17	criteria provided, single submitter	clinical testing	The c.241_252del12 variant (also known as p.I81_K84del) is located in coding exon 1 of the TBC1D24 gene. This variant results from an in-frame ATCGTGGGCAAG deletion at nucleotide positions 241 to 252. This results in the in-frame deletion of one of the IVGK repeats at codons 81 to 84. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6429 samples (12858 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae	RCV001044367	SCV001208161	pathogenic	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2023-11-18	criteria provided, single submitter	clinical testing	This variant, c.241_252del, results in the deletion of 4 amino acid(s) of the TBC1D24 protein (p.Ile81_Lys84del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs761918906, gnomAD 0.1%). This variant has been observed in individual(s) with clinical features of TBC1D24-related conditions (PMID: 29416524, 31112829, 31257402). 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 c.229_240del (p.82_84del). ClinVar contains an entry for this variant (Variation ID: 418692). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000478982	SCV003819887	pathogenic	not provided	2022-02-15	criteria provided, single submitter	clinical testing
OMIM	RCV000808206	SCV000948302	pathogenic	Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer's cramp syndrome	2019-08-09	no assertion criteria provided	literature only
Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University	RCV003984840	SCV004801115	pathogenic	Auditory neuropathy spectrum disorder	2023-04-03	no assertion criteria provided	clinical testing