ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.3445C>T (p.His1149Tyr)

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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 RCV004165505 SCV003663523 uncertain significance Cardiovascular phenotype 2022-11-10 criteria provided, single submitter clinical testing The c.3445C>T (p.H1149Y) alteration is located in exon 8 (coding exon 8) of the HCN4 gene. This alteration results from a C to T substitution at nucleotide position 3445, causing the histidine (H) at amino acid position 1149 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003505293 SCV004311181 uncertain significance Brugada syndrome 8 2023-08-03 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 2326078). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HCN4 protein function. 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. This variant has not been reported in the literature in individuals affected with HCN4-related conditions. This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1149 of the HCN4 protein (p.His1149Tyr). This variant is not present in population databases (gnomAD no frequency).

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