ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.11791G>A (p.Glu3931Lys) (rs45454496)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171798 SCV000050805 benign Cardiac arrhythmia 2013-06-24 criteria provided, single submitter research
GeneDx RCV000123649 SCV000166988 benign not specified 2017-07-25 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000123649 SCV000230676 likely benign not specified 2014-12-04 criteria provided, single submitter clinical testing
Invitae RCV001084983 SCV000252751 benign Long QT syndrome 2020-12-06 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000420423 SCV000510864 likely benign not provided 2017-01-25 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000420423 SCV000697726 likely benign not provided 2016-03-07 criteria provided, single submitter clinical testing Variant summary: Variant affects a conserved nucleotide and results in a replacement of a medium size acidic Glutamate (E) with a large size and basic Lysine (K). 2/5 in silico tool predict deleterious outcome for this change. It was found in the large and broad cohorts of NHLBI-ESP; ExAC and 1000G projects as well as in healthy control individuals in disease specific publications at a composite allele frequency of 0.26.8% which greatly exceeds the maximal allele frequency of a disease causing ANK2 allele (0.001%) indicating a benign impact. In addition, there are three homozygous individuals reported in ExAC further supporting a non-disease causing outcome. Variant was found in ARTHY patients however because of the lack of familial segregation data or comprehensive ANK2 testing these studies do not permit establishment of a cause-effect relationship between the variant and ARTHY (Mohler_PNAS_2004; Mohler_Circ_2007). One research group investigated the impact of the variant on the function of the protein and concluded that overall, the variant has negligible loss of function impact on the protein (Mohler_Circulation_2007). Clinical diagnostic centers classify variant as Benign/Likely Benign via ClinVar without evidence to independently evaluate. Taken together, evidences support a benign nature for the variant, therefore variant was classified as likely benign.
Ambry Genetics RCV000617748 SCV000736101 benign Cardiovascular phenotype 2016-06-13 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852984 SCV000995733 benign Ventricular fibrillation 2018-10-02 criteria provided, single submitter clinical testing
Mendelics RCV000019677 SCV001136764 likely benign Cardiac arrhythmia, ankyrin B-related 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000019677 SCV001309631 likely benign Cardiac arrhythmia, ankyrin B-related 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
OMIM RCV000019677 SCV000039975 uncertain significance Cardiac arrhythmia, ankyrin B-related 2004-06-15 no assertion criteria provided literature only
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058352 SCV000089872 not provided Arrhythmia no assertion provided literature only This variant has been reported as associated with Cardiac arrhythmia in the following publications (PMID:15178757). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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