ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1859G>A (p.Arg620His)

gnomAD frequency: 0.00003  dbSNP: rs746504626
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001841157 SCV001359788 uncertain significance Cardiac arrhythmia 2023-04-24 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 620 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A functional study has shown that this variant has no significant impact on channel current (PMID: 23424222). This variant has been reported in an individual affected with Brugada syndrome and in an unaffected family member (PMID: 27810048). This variant has been identified in 7/222678 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.
Invitae RCV003541290 SCV001490896 uncertain significance not provided 2023-08-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 620 of the SCN5A protein (p.Arg620His). This variant is present in population databases (rs746504626, gnomAD 0.008%). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 23424222, 32533946). ClinVar contains an entry for this variant (Variation ID: 928169). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect SCN5A function (PMID: 23424222, 32533946). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002484054 SCV002794092 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2021-09-18 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001841157 SCV004832647 uncertain significance Cardiac arrhythmia 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 620 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A functional study has shown that this variant has no significant impact on channel current (PMID: 23424222). This variant has been reported in an individual affected with Brugada syndrome and in an unaffected family member (PMID: 27810048). This variant has been identified in 7/222678 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.

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