Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000183448 | SCV000235908 | uncertain significance | not provided | 2014-08-05 | criteria provided, single submitter | clinical testing | p.Pro22Leu c.65 CCG>CTG in exon 1 of the EMD gene (NM_000117.2): A variant of unknown significance has been identified in the EMD gene. To our knowledge, the P22L variant has not been published as a mutation or as a benign polymorphism. The P22L variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is mostly conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the P22L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in DCM-CRDM panel(s). |
Labcorp Genetics |
RCV001348561 | SCV001542868 | uncertain significance | X-linked Emery-Dreifuss muscular dystrophy | 2022-02-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with EMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 201779). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 22 of the EMD protein (p.Pro22Leu). |