ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.1595T>G (p.Phe532Cys) (rs199473573)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182979 SCV000235378 uncertain significance not provided 2020-07-16 criteria provided, single submitter clinical testing Reported in individuals with various cardiac phenotypes, including paroxysmal atrial fibrillation and atrial tachycardia, sudden infant death syndrome, and incomplete right bundle branch block with overall normal EKGs (Maekawa et al., 2005; Otagiri et al., 2008; Warring et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31043699, 29728395, 15996170, 18596570, 30662450, 29062695, 28341781)
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000490338 SCV000267490 uncertain significance SUDDEN INFANT DEATH SYNDROME 2016-03-18 criteria provided, single submitter reference population
Color Health, Inc RCV001178346 SCV001342757 uncertain significance Arrhythmia 2020-12-22 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with cysteine at codon 532 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown that this variant doesn't cause significant difference in gating properties of the ion channel (PMID: 18596570). This variant has been reported in one case in the Japanese sudden infant death syndrome cohort (PMID: 18596570), one individual with arrhythmia (PMID: 15996170), one individual with suspected Brugada syndrome (PMID: 20129283), and at least one individual diagnosed with Brugada syndrome (PMID: 28341781). However, this variant has also been reported in 2 related individuals with normal electrocardiograms (ECG) exhibiting no type 1 Brugada ECG pattern or any T-wave abnormalities (PMID: 29062695). This variant has been identified in 4/247568 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058434 SCV000089954 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:15996170;PMID:18596570;PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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