ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.124G>C (p.Asp42His) (rs752597565)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000794785 SCV000934215 uncertain significance Brugada syndrome 8 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 42 of the HCN4 protein (p.Asp42His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. While this variant is present in population databases (rs752597565), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with HCN4-related disease. 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: "Not Available"; Align-GVGD: "Class C0"). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000995399 SCV001149540 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing

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