Description
This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 80 of the BEST1 protein (p.Phe80Leu). This variant is not present in population databases (gnomAD no frequency). A different variant (c.240C>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 21878505, 25082885, 26201355). This suggests that this variant is also likely to be causative of disease. ClinVar contains an entry for this variant (Variation ID: 1459557). 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.Phe80 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21878505, 25082885, 26201355, 28806213). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
