ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.2800C>T (p.Arg934Cys) (rs199638465)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000710142 SCV000223492 uncertain significance not provided 2017-08-08 criteria provided, single submitter clinical testing p.Arg934Cys (CGC>TGC): c.2800 C>T in exon 8 of the HCN4 gene (NM_005477.2). A variant of unknown significance has been identified in the HCN4 gene. The R934C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R934C variant was not observed with any significant frequency in approximately 5,700 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R934C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense mutations in nearby residues have been reported in association with Brugada syndrome, suggesting this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in ARRHYTHMIA panel(s).
Athena Diagnostics Inc RCV000710142 SCV000613592 uncertain significance not provided 2017-12-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619408 SCV000737459 likely benign Cardiovascular phenotype 2020-08-25 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV001081084 SCV000769056 likely benign Brugada syndrome 8 2020-11-04 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000710142 SCV000857591 uncertain significance not provided 2017-10-30 criteria provided, single submitter clinical testing

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