ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.1835T>C (p.Phe612Ser) (rs796053188)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189220 SCV000242852 uncertain significance not provided 2013-02-22 criteria provided, single submitter clinical testing p.Phe612Ser (TTC>TCC): c.1835 T>C in exon 12 of the SCN2A gene (NM_021007.2). The Phe612Ser missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Phe612Ser in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative as a non-polar Phenylalanine residue is replaced by a polar Serine residue. Phe612Ser alters a well conserved position in the intracellular loop between the first and second transmembrane domains of the protein, although a Serine residue has been seen in a vertebrate species. Another mutation in this loop (Asp649Asn) has been published in association with Dravet syndrome (Shi et al., 2012). However, while several in-silico algorithms predict Phe612Ser is damaging to the structure/function of the protein, another model predicts it may be non-pathogenic. Therefore, based on the currently available information, it is unclear whether Phe612Ser is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).

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