ClinVar

Description

The p.F113L pathogenic mutation (also known as c.337T>C), located in coding exon 2 of the GLA gene, results from a T to C substitution at nucleotide position 337. The phenylalanine at codon 113 is replaced by leucine, an amino acid with highly similar properties. This mutation was detected in an adult male with residual alpha-galactosidase A enzyme activity and reported cardiac-variant Fabry disease whose carrier mother also had cardiac manifestations (Eng CM et al. Mol. Med., 1997 Mar;3:174-82). Subsequently, this mutation has been reported as a Portuguese founder mutation, having been detected in multiple individuals and families with Fabry disease, frequently presenting with late-onset cardiac-variant phenotoype; however, additional features of Fabry disease in individuals with this mutation have also been reported (Spada M et al. Am. J. Hum. Genet., 2006 Jul;79:31-40; Park JY et al. Exp. Mol. Med., 2009 Jan;41:1-7; Nowak A et al. Mol. Genet. Metab., 2018 02;123:148-153; Azevedo O et al. Mol. Genet. Metab., 2019 Jul; Oliveira JP et al. Eur J Med Genet, 2019 Jun;103703). In addition, several functional assays have shown this mutation to result in reduced enzyme activity in vitro (Spada M et al. Am. J. Hum. Genet., 2006 Jul;79:31-40; Wu X et al. Hum. Mutat., 2011 Aug;32:965-77; Ishii S et al. Biochem. J., 2007 Sep;406:285-95; Park JY et al. Exp. Mol. Med., 2009 Jan;41:1-7). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.