ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.2555C>T (p.Pro852Leu) (rs779241036)

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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 RCV000326913 SCV000343606 uncertain significance not provided 2016-07-29 criteria provided, single submitter clinical testing
Invitae RCV000702797 SCV000831667 uncertain significance Brugada syndrome 8 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 852 of the HCN4 protein (p.Pro852Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs779241036, ExAC 0.006%). This variant has been observed in an individual affected with dilated cardiomyopathy and atrioventricular block; however, variants in two additional genes were also identified (PMID: 28254188). ClinVar contains an entry for this variant (Variation ID: 289273). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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.

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