ClinVar

Description

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. p.Leu479Phe (c.1435 C>T, L479F) in the NEXN gene (NM_144573.3) Given the lack of case data, the presence in the general population, and the lack of evidence for gene-phenotype relationship, we consider this variant a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has not been reported in association with disease. In silico analysis with PolyPhen-2 predicts the variant to be possibly damaging (score 0.642). Sift score is 0.95, damaging. The variant was reported online in 3 of 4075 Caucasian individuals and 0 of 1801 African-American individuals in the NHLBI Exome Sequencing Project dataset (per GeneDx report). The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. Note that other variants with strong evidence for pathogenicity have been seen at similar frequencies in this dataset so this does not necessarily rule out pathogenicity (Pan et al 2012).