Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000375362 | SCV000344752 | uncertain significance | not provided | 2016-08-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000818116 | SCV000958713 | uncertain significance | Long QT syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 3570 of the ANK2 protein (p.Glu3570Lys). This variant is present in population databases (rs180843436, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with nonexertional syncope as well as in individuals with neurodevelopmental disorders (PMID: 16253912, 28191889, 30564305). ClinVar contains an entry for this variant (Variation ID: 67595). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ANK2 protein function. 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. |
| Fulgent Genetics, |
RCV002483106 | SCV002785222 | uncertain significance | Cardiac arrhythmia, ankyrin-B-related | 2021-10-05 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004019025 | SCV003598029 | likely benign | Cardiovascular phenotype | 2023-06-26 | 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. |
| Gene |
RCV000375362 | SCV005201473 | uncertain significance | not provided | 2023-07-12 | criteria provided, single submitter | clinical testing | Described as E1452K in a teenager with long QT syndrome and an abnormal myocardial biopsy (Sherman et al., 2005); Reported in association with arrhythmia and cardiomyopathy, though limited clinical detail was provided and/or additional variants were identified (Lopes et al., 2015; Celestino-Soper et al., 2016; Proost et al., 2017); Identified among a large cohort of individuals with neurodevelopmental disorders; described as c.10804G>A (Stessman et al., 2017; Wang et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22956155, 25351510, 30564305, 33004838, 16253912, 28341588, 26771585, 28191889) |
| Cardiovascular Biomedical Research Unit, |
RCV000058340 | SCV000089860 | not provided | Congenital long QT syndrome | no assertion provided | literature only | This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16253912). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. | |
| Blueprint Genetics | RCV000143869 | SCV000188737 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2014-01-02 | no assertion criteria provided | clinical testing |