Submissions for variant NM_001199107.2(TBC1D24):c.621G>C (p.Gln207His)

dbSNP: rs876658012

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221376	SCV000272470	uncertain significance	not specified	2016-04-07	criteria provided, single submitter	clinical testing	The p.Gln207His variant in TBC1D24 has not been previously reported in individua ls with hearing loss or in large population studies. Computational prediction to ols and conservation analyses do not provide strong support for or against an im pact to the protein. In summary, the clinical significance of the p.Gln207His va riant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001853488	SCV002259862	uncertain significance	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2023-09-11	criteria provided, single submitter	clinical testing	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TBC1D24 protein function. ClinVar contains an entry for this variant (Variation ID: 229285). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 207 of the TBC1D24 protein (p.Gln207His).