Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665862 | SCV000790053 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2017-03-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001855447 | SCV002234838 | pathogenic | Walker-Warburg congenital muscular dystrophy | 2022-06-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FKRP protein in which other variant(s) (p.Ile478Thr) have been determined to be pathogenic (PMID: 16476814, 18639457, 19299310). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 550955). This variant has not been reported in the literature in individuals affected with FKRP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly219Alafs*20) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 277 amino acid(s) of the FKRP protein. |
| Ambry Genetics | RCV004026087 | SCV005028703 | pathogenic | Cardiovascular phenotype | 2023-11-28 | criteria provided, single submitter | clinical testing | The c.656delG pathogenic mutation, located in coding exon 1 of the FKRP gene, results from a deletion of one nucleotide at nucleotide position 656, causing a translational frameshift with a predicted alternate stop codon (p.G219Afs*20). This alteration occurs at the 3' terminus of theFKRP gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 56% of the protein. However, premature stop codons are typically deleterious in nature, a significant portion of the protein is affected, and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |