ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.82G>A (p.Glu28Lys)

dbSNP: rs867068803
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532717 SCV000648472 uncertain significance Brugada syndrome 8 2017-07-10 criteria provided, single submitter clinical testing In summary, this variant has uncertain impact on HCN4 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a HCN4-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces glutamic acid with lysine at codon 28 of the HCN4 protein (p.Glu28Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine.
Preventiongenetics, part of Exact Sciences RCV003403319 SCV004105822 uncertain significance HCN4-related condition 2023-03-24 criteria provided, single submitter clinical testing The HCN4 c.82G>A variant is predicted to result in the amino acid substitution p.Glu28Lys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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