Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521470 | SCV000619996 | uncertain significance | not provided | 2017-08-17 | criteria provided, single submitter | clinical testing | The L521F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L521F variant is observed in 3/11,578 (0.03%) alleles from individuals of Latino background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Labcorp Genetics |
RCV001857999 | SCV002213665 | uncertain significance | RYR1-related disorder | 2021-10-09 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 521 of the RYR1 protein (p.Leu521Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs750009277, ExAC 0.03%). This variant has not been reported in the literature in individuals with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 451318). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV002506275 | SCV002816415 | uncertain significance | Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome | 2021-09-24 | criteria provided, single submitter | clinical testing |