ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.458A>G (p.Glu153Gly) (rs560874115)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723946 SCV000224482 uncertain significance not provided 2018-09-13 criteria provided, single submitter clinical testing
Invitae RCV000232528 SCV000288913 likely benign Brugada syndrome 8 2018-01-05 criteria provided, single submitter clinical testing
GeneDx RCV000255885 SCV000321764 uncertain significance not specified 2017-02-06 criteria provided, single submitter clinical testing The E153G variant of uncertain significance in the HCN4 gene has not been published as a pathogenic variant or beenreported as a benign variant to our knowledge. The E153G variant was not observed with any significant frequency inthe 1000 Genomes project; however, data from control individuals in the NHLBI Exome Sequencing Project andExAC was not available to further assess the frequency of E153G in the general population. E153G is anon-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differin polarity, charge, size and/or other properties. However, while this substitution occurs at a position that isconserved conserved in mammals, G153 is tolerated in at least three species. Moreover, in silico analysis predicts thisvariant likely does not alter the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Ambry Genetics RCV000618430 SCV000735071 likely benign Cardiovascular phenotype 2017-04-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Does not segregate with disease in family study (genes with incomplete penetrance)
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852712 SCV000995426 likely benign Cardiomyopathy; Dilated cardiomyopathy 2019-06-11 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000157245 SCV000206972 uncertain significance Brugada syndrome 2014-10-28 no assertion criteria provided clinical testing

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