ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.2730C>A (p.Phe910Leu) (rs200814534)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000245405 SCV000320378 likely benign Cardiovascular phenotype 2020-06-04 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
Invitae RCV001088501 SCV000541556 likely benign Brugada syndrome 8 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000711890 SCV000620379 uncertain significance not provided 2017-08-23 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the HCN4 gene. The F910L variant has been previously reported in at least two Spanish male individuals with sudden cardiac death occurring in their 40's (Sanchez et al., 2016; Campuzano et al., 2017); however, no family history details or segregation studies were reported. This variant is observed in 2/1014 (0.20%) alleles from individuals of Latino ancestry, and in 3/15912 (0.02%) alleles from individuals of Non-Finnish European ancestry, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, although this substitution occurs at a position that is conserved in mammals, F910L is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Lastly, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Athena Diagnostics Inc RCV000711890 SCV000842301 uncertain significance not provided 2018-06-15 criteria provided, single submitter clinical testing

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