ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.433C>G (p.Pro145Ala) (rs886043525)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000346829 SCV000340535 uncertain significance not provided 2016-03-31 criteria provided, single submitter clinical testing
Invitae RCV000647230 SCV000769019 uncertain significance Brugada syndrome 8 2020-08-26 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 145 of the HCN4 protein (p.Pro145Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. 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 variant has not been reported in the literature in individuals with HCN4-related disease. ClinVar contains an entry for this variant (Variation ID: 286934). 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: Benign; 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.

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