Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000213644 | SCV000272199 | uncertain significance | not specified | 2015-09-10 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Thr69Ala vari ant in NEBL has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.2% (23/11558) of Latino chromosomes by the Exome A ggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs780384504). Computational prediction tools and conservation analysis suggest that the p.Thr 69Ala variant may not impact the protein, though this information is not predict ive enough to rule out pathogenicity. In summary, while the clinical significanc e of the p.Thr69Ala variant is uncertain, these data suggest that it is more lik ely to be benign. |
| Invitae | RCV000233812 | SCV000289523 | likely benign | Primary dilated cardiomyopathy | 2024-01-13 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000620613 | SCV000739908 | uncertain significance | Cardiovascular phenotype | 2013-09-19 | criteria provided, single submitter | clinical testing | The p.T69A variant (also known as c.205A>G) is located in coding exon 3 of the NEBL gene. This alteration results from an A to G substitution at nucleotide position 205. The threonine at codon 69 is replaced by alanine, an amino acid with some similar properties. No population frequency information could be found. ​This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. This amino acid position is poorly conserved on sequence alignment. This variant is predicted to be benign by PolyPhen and tolerated by SIFT in silico analyses. Since supporting evidence is limited at this time, the clinical significance of p.T69A remains unclear. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000213644 | SCV000280396 | uncertain significance | not specified | 2013-09-20 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. NEBL p.The69Ala (c.205A>G) This variant is novel. The variant is located in coding exon 3 of the NEBL gene. The threonine is replaced by alanine, an amino acid with similar properties. In silico analysis with PolyPhen-2 predicts the variant to be benign and tolerated by SIFT. Mutation taster predicts this variant to be a polymorphism. The threonine at codon 69 is poorly conserved across species. No other variants have been reported in association with disease at this codon or at nearby codons. In total the variant has not been seen in ~6,500 individuals from publicly available population datasets. There is no variation at codon 69 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,500 Caucasian and African American individuals (as of 9/20/13). Note that this dataset does not match the patient's ancestry (Mexico). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 9/20/13). |