ClinVar Miner

Submissions for variant NM_002234.4(KCNA5):c.1733G>A (p.Arg578Lys) (rs12720445)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171809 SCV000050821 benign not specified 2013-06-24 criteria provided, single submitter research
Invitae RCV000528153 SCV000646983 benign Atrial fibrillation, familial, 7 2020-12-04 criteria provided, single submitter clinical testing
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000584775 SCV000692521 benign Brugada syndrome 1 2017-03-16 criteria provided, single submitter research The KCNA5 Arg578Lys has been previously identified in 2/95 "white" controls, in this study the variant did not affect potassium channel gating in transfected hamster oocytes, but did cause resistance to Quinidine (Simard C, et al., 2005). This KCNA5 Arg578Lys variant is found in the Exome Aggregation Consortium dataset at an elevated frequency (MAF=0.005; http://exac.broadinstitute.org/), suggesting that it is a common polymorphism (Ng, D et al., 2013). We identified this variant in one proband with Brugada syndrome, who has a normal QT and no family history of disease or SCD. Furthermore, computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to be well tolerated. In summary, based on the presence of KCNA5 Arg578Lys in controls, a high population frequency, and in silico tools predicting no deleterious affect on the protein, we classify this variant as "benign".
Illumina Clinical Services Laboratory,Illumina RCV000528153 SCV001270769 uncertain significance Atrial fibrillation, familial, 7 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000528153 SCV001473129 likely benign Atrial fibrillation, familial, 7 2020-05-29 criteria provided, single submitter clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001572979 SCV001798186 likely benign not provided no assertion criteria provided clinical testing

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