Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003794193 | SCV004584719 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-03-13 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 2070 of the DSP protein (p.Asp2070His). |
All of Us Research Program, |
RCV004006046 | SCV004836270 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2023-12-18 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with histidine at codon 2070 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a 10 year old male affected with myofibrillar myopathy with cardiopulmonary involvement (slightly decreased vital capacity at spirometry, supraventricular wandering, and a pacemaker) (PMID: 33652732). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |