Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000538326 | SCV000649609 | likely pathogenic | Qualitative or quantitative defects of dysferlin | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 52 of the DYSF protein (p.Trp52Arg). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 471280). A different variant (c.154T>C) giving rise to the same protein effect has been determined to be pathogenic (PMID: 1707005, 18853459, 22194990). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). |