Submissions for variant NM_004183.4(BEST1):c.1067G>A (p.Arg356Gln)

dbSNP: rs751707411

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000425735	SCV000533922	uncertain significance	not provided	2016-12-05	criteria provided, single submitter	clinical testing	The R356Q variant in the BEST1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R356Q variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R356Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R356Q as a variant of uncertain significance.
Noruzinia Laboratory, Tarbiat Modares University	RCV000850038	SCV000965598	uncertain significance	Cone-rod dystrophy 6		criteria provided, single submitter	clinical testing	This variant possibly associates with a pathogenic mutation in GUCY2D to develop Cone-rod dystrophy-6 disease. It is possible to hypothesize a double heterozygosity scenario to explain the condition. The c.887G>A variant is present in heterozygote state in healthy participants.
Invitae	RCV000425735	SCV001567596	uncertain significance	not provided	2023-04-09	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) 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 BEST1 protein function. ClinVar contains an entry for this variant (Variation ID: 390960). This variant has not been reported in the literature in individuals affected with BEST1-related conditions. This variant is present in population databases (rs751707411, gnomAD 0.05%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 356 of the BEST1 protein (p.Arg356Gln).