Submissions for variant NM_033028.5(BBS4):c.617C>A (p.Thr206Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003635290	SCV004450708	uncertain significance	Bardet-Biedl syndrome	2023-11-03	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 206 of the BBS4 protein (p.Thr206Lys). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with BBS4-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BBS4 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	RCV004723423	SCV005339746	uncertain significance	BBS4-related disorder	2024-08-16	no assertion criteria provided	clinical testing	The BBS4 c.617C>A variant is predicted to result in the amino acid substitution p.Thr206Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.