Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000671966 | SCV000797013 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2018-01-09 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002233101 | SCV002511874 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2022-04-01 | criteria provided, single submitter | clinical testing | 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. |
| Ambry Genetics | RCV003163067 | SCV003870499 | likely pathogenic | Cardiovascular phenotype | 2023-03-02 | criteria provided, single submitter | clinical testing | The c.1415delA variant, located in coding exon 1 of the FKRP gene, results from a deletion of one nucleotide at nucleotide position 1415, causing a translational frameshift with a predicted alternate stop codon (p.K472Sfs*18). This alteration occurs at the 3' terminus of theFKRP gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 24 amino acids (~5%) 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 majority of available evidence to date, this variant is likely to be pathogenic. |
| Baylor Genetics | RCV003459632 | SCV004197446 | likely pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 | 2022-10-03 | criteria provided, single submitter | clinical testing |