Submissions for variant NM_001199107.2(TBC1D24):c.1015A>G (p.Asn339Asp)

gnomAD frequency: 0.00002  dbSNP: rs574768683

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118581	SCV000152987	uncertain significance	not provided	2014-01-14	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000606977	SCV000731782	uncertain significance	not specified	2017-07-13	criteria provided, single submitter	clinical testing	The p.Asn339Asp variant in TBC1D24 has not been previously reported in individua ls with hearing loss, but has been reported in ClinVar (Variation ID# 130541) as of uncertain significance. It has also been identified in 43/272092 chromosomes with the highest frequency 19/29928 of South Asian chromosomes by the Genome Ag gregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs574768683) ; however, its frequency is not high enough to rule out a pathogenic role. Compu tational prediction tools and conservation analyses do not provide strong suppor t for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain.
Invitae	RCV000811630	SCV000951905	likely benign	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000118581	SCV001820281	uncertain significance	not provided	2023-07-26	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003343646	SCV004061357	uncertain significance	Inborn genetic diseases	2023-09-12	criteria provided, single submitter	clinical testing	The c.1015A>G (p.N339D) alteration is located in exon 4 (coding exon 3) of the TBC1D24 gene. This alteration results from a A to G substitution at nucleotide position 1015, causing the asparagine (N) at amino acid position 339 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000118581	SCV004144808	uncertain significance	not provided	2023-10-01	criteria provided, single submitter	clinical testing	TBC1D24: PM2