Submissions for variant NM_001148.6(ANK2):c.3366C>T (p.Asn1122=)

gnomAD frequency: 0.00256  dbSNP: rs114896457

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001085741	SCV000286244	benign	Long QT syndrome	2024-01-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590762	SCV000697735	benign	not provided	2016-04-04	criteria provided, single submitter	clinical testing	Variant Summary: The variant of interest causes a synonymous change involving a non-conserved nucleotide with 5/5 in silico programs via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 169/121394 (1/718), which significantly exceeds the predicted maximum expected allele frequency for a pathogenic ANK2 variant of 1/100000. The variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical laboratories, to our knowledge. Therefore, taking into consideration the nature of this variant being a synonymous change and the high frequency in controls, it is classified as Benign.
Ambry Genetics	RCV000620078	SCV000735739	benign	Cardiovascular phenotype	2017-01-21	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590762	SCV000885007	benign	not provided	2017-12-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001149718	SCV001310700	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	RCV000590762	SCV001852107	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001149718	SCV002525029	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590762	SCV004148726	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BP7, BS2
Clinical Genetics, Academic Medical Center	RCV001699161	SCV001918234	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001699161	SCV001929602	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699161	SCV001952616	benign	not specified		no assertion criteria provided	clinical testing