Submissions for variant NM_001199107.2(TBC1D24):c.1302+1G>T

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV004550676	SCV004103694	likely pathogenic	TBC1D24-related disorder	2023-08-30	criteria provided, single submitter	clinical testing	The TBC1D24 c.1302+1G>T variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2549932-G-T). Variants that disrupt the consensus splice donor site in TBC1D24 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003778229	SCV004593734	likely pathogenic	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2023-02-16	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change affects a donor splice site in intron 6 of the TBC1D24 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TBC1D24 are known to be pathogenic (PMID: 23526554, 24291220). This variant is present in population databases (rs767616057, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions.