Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000214544 | SCV000272202 | uncertain significance | not specified | 2015-05-18 | criteria provided, single submitter | clinical testing | The p.Ser863Cys variant in NEBL has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/10326 African chromosomes and 2/66490 European chromosomes by the Exome Aggregation Consortium (ExAC, http://e xac.broadinstitute.org; dbSNP rs150152361). Computational prediction tools and c onservation analysis suggest that this variant may impact the protein, though th is information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Ser863Cys variant is uncertain. |
Labcorp Genetics |
RCV000822758 | SCV000963574 | uncertain significance | Primary dilated cardiomyopathy | 2019-06-20 | 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. 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: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with NEBL-related disease. ClinVar contains an entry for this variant (Variation ID: 229046). This variant is present in population databases (rs150152361, ExAC 0.01%). This sequence change replaces serine with cysteine at codon 863 of the NEBL protein (p.Ser863Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. |