Submissions for variant NM_001148.6(ANK2):c.6176C>T (p.Thr2059Met)

gnomAD frequency: 0.00058  dbSNP: rs200765866

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171741	SCV000055256	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Invitae	RCV000195655	SCV000253358	likely benign	Long QT syndrome	2023-11-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625123	SCV000447192	likely benign	Cardiac arrhythmia, ankyrin-B-related	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV000171741	SCV000516837	likely benign	not provided	2021-02-05	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25351510, 28086167, 23861362, 17242276)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000171741	SCV000697741	likely benign	not provided	2016-08-29	criteria provided, single submitter	clinical testing	Variant summary: The ANK2 c.6176C>T (p.Thr2059Met) variant involves the alteration of a non-conserved nucleotide. 2/3 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 86/120790 control chromosomes at a frequency of 0.000712, which is approximately 71 times the estimated maximal expected allele frequency of a pathogenic ANK2 variant (0.00001), suggesting this variant is likely a benign polymorphism. It was detected on one HCM patient (Lopes_2015) without strong evidence for pathogenicity. There are no published functional studies for the variant. One clinical diagnostic laboratory and a research institution have classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Ambry Genetics	RCV000618281	SCV000736402	likely benign	Cardiovascular phenotype	2018-07-09	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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625123	SCV000743823	likely benign	Cardiac arrhythmia, ankyrin-B-related	2016-09-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000171741	SCV004148739	benign	not provided	2022-04-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003954996	SCV004770733	likely benign	ANK2-related condition	2020-03-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000171741	SCV001925135	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001729424	SCV001954189	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000171741	SCV001966875	likely benign	not provided		no assertion criteria provided	clinical testing