Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000489159 | SCV000331850 | pathogenic | not provided | 2015-08-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000489159 | SCV000577688 | uncertain significance | not provided | 2024-05-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge |
Blueprint Genetics | RCV000489159 | SCV000928061 | likely pathogenic | not provided | 2018-11-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001321146 | SCV001511965 | uncertain significance | Desmin-related myofibrillar myopathy | 2020-07-09 | criteria provided, single submitter | clinical testing | This sequence change affects codon 245 of the DES mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DES protein. This variant also falls at the last nucleotide of exon 3 of the DES coding sequence, which is part of the consensus splice site for this exon. 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. Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with DES-related conditions. ClinVar contains an entry for this variant (Variation ID: 281234). This variant is not present in population databases (ExAC no frequency). |