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

gnomAD frequency: 0.00235  dbSNP: rs45454496

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV001841251	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.
Eurofins Ntd Llc (ga)	RCV000123649	SCV000230676	likely benign	not specified	2014-12-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084983	SCV000252751	benign	Long QT syndrome	2024-01-31	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	This alteration is classified as 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.
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 Laboratory Services, 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.
Genome-Nilou Lab	RCV000019677	SCV002525103	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000420423	SCV004148771	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000420423	SCV005256072	likely benign	not provided		criteria provided, single submitter	not provided
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	RCV001841251	SCV000089872	not provided	Cardiac 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.
PreventionGenetics, part of Exact Sciences	RCV003974846	SCV004799590	benign	ANK2-related disorder	2019-05-07	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).