Submissions for variant NM_001040142.2(SCN2A):c.1577C>T (p.Ser526Leu)

gnomAD frequency: 0.00001  dbSNP: rs749504084

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189245	SCV000242877	uncertain significance	not provided	2014-10-20	criteria provided, single submitter	clinical testing	The S526Lvariant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S526L 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. This substitution occurs at a conserved position in the cytoplasmic loop between the first and second homologous domains; however, Leucine is observed at this position in one distantly related species. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in EPILEPSY panel(s).
Ambry Genetics	RCV002514060	SCV003557204	uncertain significance	Inborn genetic diseases	2021-06-21	criteria provided, single submitter	clinical testing	The c.1577C>T (p.S526L) alteration is located in exon 11 (coding exon 10) of the SCN2A gene. This alteration results from a C to T substitution at nucleotide position 1577, causing the serine (S) at amino acid position 526 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.