Submissions for variant NM_004183.4(BEST1):c.79A>G (p.Ser27Gly)

dbSNP: rs2134409684

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001990454	SCV002257330	likely pathogenic	not provided	2021-02-03	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with glycine at codon 27 of the BEST1 protein (p.Ser27Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine. This variant has been observed in individual(s) with autosomal dominant Best disease (Invitae). 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 expected to disrupt BEST1 protein function. This variant disrupts the p.Ser27 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31570112, 28127548, 10854112). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.