ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.2650C>A (p.Pro884Thr) (rs745819208)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619207 SCV000735690 uncertain significance Cardiovascular phenotype 2016-12-29 criteria provided, single submitter clinical testing The p.P884T variant (also known as c.2650C>A), located in coding exon 8 of the HCN4 gene, results from a C to A substitution at nucleotide position 2650. The proline at codon 884 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is well conserved on limited sequence alignment; however, threonine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001298618 SCV001487680 uncertain significance Brugada syndrome 8 2020-03-14 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 884 of the HCN4 protein (p.Pro884Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 518606). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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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