ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.1376A>C (p.Glu459Ala) (rs184769423)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000189212 SCV000152614 likely benign not specified 2016-05-12 criteria provided, single submitter clinical testing
GeneDx RCV000189212 SCV000242844 uncertain significance not specified 2017-07-21 criteria provided, single submitter clinical testing The E459A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E459A variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project and the 1000 Genomes Project. This substitution occurs at a position predicted to be within the intracellular loop between the first and second homologous domain where amino acids with similar properties to Glutamic acid are tolerated across species. However, the E459A 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678841 SCV000805030 uncertain significance Pyridoxine-dependent epilepsy 2017-04-21 criteria provided, single submitter clinical testing
Invitae RCV000733650 SCV000814993 likely benign not provided 2019-02-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000719876 SCV000850747 likely benign History of neurodevelopmental disorder 2018-03-16 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;In silico models in agreement (benign)
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000733650 SCV000861740 uncertain significance not provided 2018-06-14 criteria provided, single submitter clinical testing

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