ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.1636G>A (p.Asp546Asn) (rs370884239)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558117 SCV000648437 uncertain significance Brugada syndrome 8 2020-09-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 546 of the HCN4 protein (p.Asp546Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs370884239, ExAC 0.006%). This variant has been observed in an individual who suffered a sudden unexplained death (PMID: 29247119). ClinVar contains an entry for this variant (Variation ID: 470650). This variant has been reported to affect HCN4 protein function (PMID: 30578647). 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.
GeneDx RCV001564440 SCV001787608 uncertain significance not provided 2021-03-30 no assertion criteria provided clinical testing Reported in a patient with sudden infant death syndrome (Lin et al., 2017); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 470650; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Functional studies suggest the presence of this variant may alter channel function; however, it is not known whether these findings are biological or clinically relevant in vivo (Dong et al., 2019); This variant is associated with the following publications: (PMID: 30391667, 29247119, 30578647)

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