ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.10708G>A (p.Glu3570Lys)

gnomAD frequency: 0.00005  dbSNP: rs180843436
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000375362 SCV000344752 uncertain significance not provided 2016-08-16 criteria provided, single submitter clinical testing
Invitae RCV000818116 SCV000958713 uncertain significance Long QT syndrome 2023-10-04 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, Fulgent Genetics RCV002483106 SCV002785222 uncertain significance Cardiac arrhythmia, ankyrin-B-related 2021-10-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002514292 SCV003598029 likely benign Inborn genetic diseases 2023-06-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust 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

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