ClinVar Miner

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

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Total submissions: 8
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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 RCV001082507 SCV000288913 likely benign Brugada syndrome 8 2020-12-04 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 2018-07-22 criteria provided, single submitter clinical testing Does not segregate with disease in family study (genes with incomplete penetrance);In silico models in agreement (benign)
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852712 SCV000995426 likely benign Primary dilated cardiomyopathy; Cardiomyopathy 2019-06-11 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001117433 SCV001275619 uncertain significance Sick sinus syndrome 2, autosomal dominant 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Blueprint Genetics RCV000157245 SCV000206972 uncertain significance Brugada syndrome 2014-10-28 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000723946 SCV001742089 likely benign not provided no assertion criteria provided clinical testing

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