Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000696096 | SCV000824643 | uncertain significance | Long QT syndrome | 2021-04-14 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with glycine at codon 2516 of the ANK2 protein (p.Ser2516Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ANK2-related disease. This variant is present in population databases (rs771826064, ExAC 0.002%). |
| Gene |
RCV001775966 | SCV002013121 | uncertain significance | not provided | 2020-09-16 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 574222; Landrum et al., 2016); Located in exon 38 which is expressed in brain-specific ANK2 transcripts; no pathogenic variants in exon 38 have been reported in association with cardiac phenotypes to our knowledge |
| Ambry Genetics | RCV002388264 | SCV002674042 | likely benign | Cardiovascular phenotype | 2020-11-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |