ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.3206G>A (p.Arg1069Gln)

gnomAD frequency: 0.00001  dbSNP: rs760242560
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002044349 SCV002109999 uncertain significance Brugada syndrome 8 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1069 of the HCN4 protein (p.Arg1069Gln). This variant is present in population databases (rs760242560, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1348490). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt HCN4 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002324224 SCV002609326 uncertain significance Cardiovascular phenotype 2023-12-31 criteria provided, single submitter clinical testing The p.R1069Q variant (also known as c.3206G>A), located in coding exon 8 of the HCN4 gene, results from a G to A substitution at nucleotide position 3206. The arginine at codon 1069 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002478099 SCV002781553 uncertain significance Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 2021-09-28 criteria provided, single submitter clinical testing

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