ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.2194G>A (p.Gly732Ser) (rs199530458)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171644 SCV000055268 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV000822988 SCV000963820 uncertain significance Brugada syndrome 8 2018-10-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 732 of the HCN4 protein (p.Gly732Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs199530458, ExAC 0.002%). This variant has not been reported in the literature in individuals with HCN4-related disease. ClinVar contains an entry for this variant (Variation ID: 191452). 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 C55"). 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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