Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002010793 | SCV002296164 | likely pathogenic | Desmin-related myofibrillar myopathy | 2021-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with serine at codon 405 of the DES protein (p.Tyr405Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with clinical features of DES-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). |