Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001058324 | SCV001222884 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2023-06-17 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 853504). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. This variant is present in population databases (rs779173447, gnomAD 0.01%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 329 of the PKP2 protein (p.Ser329Cys). |
| Color Diagnostics, |
RCV001185885 | SCV001352194 | uncertain significance | Cardiomyopathy | 2021-04-20 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with cysteine at codon 329 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 12/250014 chromosomes 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. |