Submissions for variant NM_017752.3(TBC1D8B):c.427G>A (p.Ala143Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002949729	SCV003284761	uncertain significance	not provided	2024-07-05	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 143 of the TBC1D8B protein (p.Ala143Thr). This variant is present in population databases (rs141400138, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TBC1D8B-related conditions. ClinVar contains an entry for this variant (Variation ID: 2073080). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
PreventionGenetics, part of Exact Sciences	RCV003898656	SCV004709337	likely benign	TBC1D8B-related disorder	2023-12-04	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).