ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.3305G>A (p.Arg1102His)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703047 SCV000831928 uncertain significance Brugada syndrome 8 2018-09-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1102 of the HCN4 protein (p.Arg1102His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs548130184, ExAC 0.04%). This variant was reported in an individual that suffered a sudden cardiac death (PMID: 28086167). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine 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 RCV000763981 SCV000894932 uncertain significance Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8 2018-10-31 criteria provided, single submitter clinical testing

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