Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000038090 | SCV000061756 | uncertain significance | not specified | 2011-12-21 | criteria provided, single submitter | clinical testing | The Ile2530Phe variant (DSP) has not been previously reported nor previously ide ntified by our laboratory. Isoleucine (Ile) at position 2530 is moderately conse rved in evolutionarily distant species (frog has a valine (Val) at this position ), and this information is insufficient to predict if a change would impact the protein. Computational tools (PolyPhen2, SIFT) predict that a change to phenylal anine (Phe) would impact the protein, though the accuracy of these tools is unkn own. Additional information is needed to fully assess the clinical significance of the Ile2530Phe variant. |
Invitae | RCV001307432 | SCV001496844 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2020-06-29 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with phenylalanine at codon 2530 of the DSP protein (p.Ile2530Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 44954). 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: "Benign"; Align-GVGD: "Class C0"). 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. |