ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.694G>A (p.Val232Ile) (rs45471994)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724673 SCV000231827 uncertain significance not provided 2015-03-20 criteria provided, single submitter clinical testing
GeneDx RCV000724673 SCV000235340 likely benign not provided 2021-06-22 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23414114, 25637381, 24136861, 24055113, 18599870, 20129283, 29728395, 31535183, 26582918)
Invitae RCV000058840 SCV000291832 likely benign Brugada syndrome 2020-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000246365 SCV000320149 uncertain significance Cardiovascular phenotype 2019-08-01 criteria provided, single submitter clinical testing The p.V232I variant (also known as c.694G>A), located in coding exon 5 of the SCN5A gene, results from a G to A substitution at nucleotide position 694. The valine at codon 232 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported in two individuals from a Brugada syndrome cohort (Kapplinger et al. Heart Rhythm. 2010;7(1):33-46). This variant was also described in conjunction with SCN5A p.L1308F in two other individuals, one diagnosed with lidocaine-induced Brugada syndrome and the second with lignocaine-induced CNS toxicity (Barajas-Martinez HM et al. Circ Res. 2008;103(4):396-404; Hayaran N et al. J Clin Anesth. 2017;36:36-38). Barajas-Martinez HM et al (2008) performed in vitro functional analyses in human cells and demonstrated that sodium channel function in V232I/L1308F cells is similar to that in wild-type cells in the absence of lidocaine. In the presence of lidocaine, V232I/L1308F cells exhibited sodium channel function abnormalities; however, the effects of V232I alone were significantly less. The p.V232I variant has also been detected in exome cohorts, but cardiovascular history was not provided (Dorschner MO et al. Am J Hum Genet. 2013; Risgaard B et al. Clin Genet. 2013;84(5):489-95; 93(4):631-40; Amendola LM et al. Genome Res. 2015;25(3):305-15). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mendelics RCV000987235 SCV001136485 uncertain significance Brugada syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV001175638 SCV001339311 likely benign Arrhythmia 2019-01-15 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000724673 SCV001714698 uncertain significance not provided 2021-02-11 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058840 SCV000090360 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:18599870;PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
CSER _CC_NCGL, University of Washington RCV000148856 SCV000190600 uncertain significance Brugada syndrome, lidocaine-induced 2014-06-01 no assertion criteria provided research

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