Submissions for variant NM_001148.6(ANK2):c.3543C>T (p.Ala1181=)

gnomAD frequency: 0.00265  dbSNP: rs76685232

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001085742	SCV000286245	benign	Long QT syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586886	SCV000697736	benign	not provided	2016-04-04	criteria provided, single submitter	clinical testing	Variant summary: The vriant affects a non-conserved nucleotide and results in synonymous mutation. Mutation taster predicts a disease causing outcome for this change while 5/5 in silico tools via Alamut predict no impact on splicing. The variant was observed in the large and broad cohorts of the NHLBI-ES and ExAC projects at an allele frequency of 0.15% which greatly exceeds (~150 times) the maximal expected allele frequency of a disease causing ANK2 allele (0.001%), strongly supporting a benign nature for the variant. Based on the high allele frequency in the general population, the variant was classified as Benign.
Ambry Genetics	RCV000620603	SCV000737428	likely benign	Cardiovascular phenotype	2017-08-31	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586886	SCV000885008	benign	not provided	2017-12-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001145403	SCV001306073	likely benign	Cardiac arrhythmia, ankyrin-B-related	2018-01-12	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	RCV000586886	SCV001860794	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001145403	SCV002525032	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586886	SCV004148727	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BP7, BS2
Clinical Genetics, Academic Medical Center	RCV001699162	SCV001921883	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001699162	SCV001929127	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699162	SCV001956947	benign	not specified		no assertion criteria provided	clinical testing