ClinVar

Description

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. This variant disrupts the p.Arg66 amino acid residue in CASR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16740594, 25104082). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects CASR function (PMID: 8702647, 16740594, 17284438, 21239511). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 8335). This variant is also known as p.Arg67Cys. This missense change has been observed in individual(s) with CASR-related conditions (PMID: 7726161, 16740594). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 66 of the CASR protein (p.Arg66Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine.