Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Agnes Ginges Centre for Molecular Cardiology, |
RCV000201903 | SCV000256649 | uncertain significance | Paroxysmal familial ventricular fibrillation | 2015-08-12 | criteria provided, single submitter | research | The DSP Tyr2396Asn is a novel variant. It is absent from both the 1000 genomes project (http://www.1000genomes.org/), and the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). We identified this variant in a clinically unaffected female, whose brother has idiopathic VF. Both patients also have a second variant (LMNA Thr27Ser) which is classified as a variant of "uncertain significance". Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to have a deleterious effect. Based on its absence in the general population and our limited familial data, we classify DSP Tyr2396Asn as variant of "uncertain significance". |
Invitae | RCV002515479 | SCV003352257 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2022-04-20 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 2396 of the DSP protein (p.Tyr2396Asn). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 217831). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |