Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000218451 | SCV000272206 | uncertain significance | not specified | 2016-01-26 | criteria provided, single submitter | clinical testing | The c.903+1G>T variant in NEBL has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 5/10364 African chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/; dbSNP rs7 75057540). This variant occurs in the invariant region (+/- 1,2) of the splice c onsensus sequence and is predicted to cause altered splicing leading to an abnor mal or absent protein. While missense variants in NEBL have been reported in ind ividuals with DCM and endocardial fibroelastosis (Purevjav 2010), the spectrum o f pathogenic variation has not been fully elucidated and it is unclear if this v ariant will contribute to disease. In summary, the clinical significance of the c.903+1G>T variant is uncertain. |
Invitae | RCV001853471 | SCV002149900 | uncertain significance | Primary dilated cardiomyopathy | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 9 of the NEBL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NEBL cause disease. This variant is present in population databases (rs775057540, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 229050). 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. |