ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.1703G>C (p.Ser568Thr) (rs138714806)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185509 SCV000223488 uncertain significance not specified 2016-11-15 criteria provided, single submitter clinical testing The S568T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, this variant has been identified in other individuals who underwent genetic testing for arrhythmia at GeneDx and has been reported as a variant of uncertain significance in ClinVar by an outside laboratory. The NHLBI Exome Sequencing Project and the 1000 Genomes Project reports S568T was observed in 0.1-0.15% of alleles from individuals of European background. The S568T variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Serine are tolerated across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, no missense variants in nearby residues have been reported in the Human Gene Mutation Database (Stenson et al., 2014), indicating that this region of the gene is not known to harbor disease-causing variants. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000185509 SCV000231083 likely benign not specified 2015-09-17 criteria provided, single submitter clinical testing
Invitae RCV000234448 SCV000288899 likely benign Brugada syndrome 8 2017-11-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620504 SCV000735825 uncertain significance Cardiovascular phenotype 2016-09-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence

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