ClinVar

Description

A variant of uncertain significance has been identified in the FKRP gene. The c.957_958delGCinsAA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 5,600 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 c.957_958delGCinsAA variant is caused by two nucleotide substitutions (c.957 G>A and c.958 C>A) on the same allele (in cis), resulting in an in-frame deletion of a single Arginine residue and the insertion of a single Serine residue at amino acid position 320, denoted R320S. The R320S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.