ClinVar

Description

Variant summary: FKRP c.1415delA (p.Lys472SerfsX18) located in the last exon results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. At-least one truncation downstream of this position has been classified as pathogenic by our laboratory (c.1486T>A, p.*496R) and also reported in association with Limb-Girdle Muscular Dystrophy in the HGMD database (example, c.1475delC, p.Thr492Argfs*28). The variant was absent in 241018 control chromosomes. To our knowledge, no occurrence of c.1415delA in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.