ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.3028G>T (p.Ala1010Ser)

gnomAD frequency: 0.00001  dbSNP: rs748634893
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000706376 SCV000835421 uncertain significance Brugada syndrome 8 2024-10-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1010 of the HCN4 protein (p.Ala1010Ser). This variant is present in population databases (no rsID available, gnomAD 0.03%). 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: 582329). 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.
GeneDx RCV001772010 SCV002003154 uncertain significance not provided 2020-07-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 582329; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics RCV002440546 SCV002753114 uncertain significance Cardiovascular phenotype 2022-08-11 criteria provided, single submitter clinical testing The c.3028G>T (p.A1010S) alteration is located in exon 8 (coding exon 8) of the HCN4 gene. This alteration results from a G to T substitution at nucleotide position 3028, causing the alanine (A) at amino acid position 1010 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002485771 SCV002778990 uncertain significance Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 2021-12-22 criteria provided, single submitter clinical testing

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