ClinVar Miner

Submissions for variant NM_002234.4(KCNA5):c.381C>T (p.Ser127=)

gnomAD frequency: 0.02823  dbSNP: rs45504599
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000555990 SCV000379697 likely benign Atrial fibrillation, familial, 7 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 RCV000555990 SCV000646991 benign Atrial fibrillation, familial, 7 2024-02-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000555990 SCV001473228 benign Atrial fibrillation, familial, 7 2023-09-30 criteria provided, single submitter clinical testing
GeneDx RCV001675792 SCV001894001 benign not provided 2020-09-23 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28768485, 24068186, 15735608)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001699303 SCV003929277 benign not specified 2023-04-05 criteria provided, single submitter clinical testing Variant summary: KCNA5 c.381C>T alters a non-conserved nucleotide resulting in a synonymous change. 4/4 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 0.026 in 249732 control chromosomes in the gnomAD database, including 115 homozygotes. The observed variant frequency is approximately 275-fold of the estimated maximal expected allele frequency for a pathogenic variant in KCNA5 causing Atrial Fibrillation phenotype (9.4e-05), strongly suggesting that the variant is benign. c.381C>T has been reported in the literature in individuals affected with Atrial Fibrillation or pulmonary arterial hypertension without evidence of causality and with other co-occurring variants (Winkel_2011, Wang_2016). These reports do not provide unequivocal conclusions about association of the variant with Atrial Fibrillation. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Clinical Genetics, Academic Medical Center RCV001699303 SCV001918879 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001699303 SCV001956802 benign not specified no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.