ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.3148G>A (p.Gly1050Arg) (rs1443227484)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000995389 SCV001149523 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing
Invitae RCV001053613 SCV001217885 uncertain significance Brugada syndrome 8 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1050 of the HCN4 protein (p.Gly1050Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with HCN4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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