ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.3392G>A (p.Ser1131Asn)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV003448593 SCV004176113 uncertain significance Sick sinus syndrome 2, autosomal dominant; Epilepsy, idiopathic generalized, susceptibility to, 18 2023-06-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005062951 SCV005724915 uncertain significance Brugada syndrome 8 2024-09-23 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1131 of the HCN4 protein (p.Ser1131Asn). This variant is not present in population databases (gnomAD no frequency). 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: 2665043). 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.

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