Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000459118 | SCV000552183 | uncertain significance | Desmin-related myofibrillar myopathy | 2021-09-14 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the c.735+3 nucleotide in the DES gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 11073539, 23155419). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 411151). This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 3 of the DES gene. It does not directly change the encoded amino acid sequence of the DES protein. It affects a nucleotide within the consensus splice site of the intron. |