ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.3118G>A (p.Gly1040Arg) (rs199473186)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540482 SCV000637121 uncertain significance Brugada syndrome 2017-06-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1040 of the SCN5A protein (p.Gly1040Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs199473186, ExAC 0.02%). This variant has been reported in multiple control individuals (PMID: 20129283, 19841300, 15851227, 25904541). ClinVar contains an entry for this variant (Variation ID: 67779). This variant identified in the SCN5A gene is located in the interdomain linker DII/DIII region of the resulting protein (PMID: 25348405, 12650879), but it is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000765736 SCV000897104 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1, autosomal recessive; Progressive familial heart block, type 1A; Paroxysmal familial ventricular fibrillation 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2018-10-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV001180819 SCV001345843 uncertain significance Arrhythmia 2019-12-06 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058550 SCV000090070 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19841300;PMID:20129283).

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