ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.11538C>T (p.Leu3846=) (rs45602336)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000178518 SCV000230613 uncertain significance not provided 2015-02-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000249867 SCV000320296 likely benign Cardiovascular phenotype 2015-10-08 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Illumina Clinical Services Laboratory,Illumina RCV001094817 SCV000447232 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.
Invitae RCV000334502 SCV000557238 benign Long QT syndrome 2020-11-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779701 SCV000916454 benign not specified 2018-11-05 criteria provided, single submitter clinical testing Variant summary: ANK2 c.11538C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00044 in 276408 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 44-fold above the estimated maximal expected allele frequency for a pathogenic variant in ANK2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.11538C>T in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation with conflicting interpretations (2x - VUS; 2x likely benign/benign). Based on the evidence outlined above, the variant was classified as benign.

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