Submissions for variant NM_001130438.3(SPTAN1):c.6496C>T (p.Arg2166Cys) (rs775190610)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189529	SCV000243172	uncertain significance	not provided	2013-03-28	criteria provided, single submitter	clinical testing	p.Arg2166Cys (CGC>TGC): c.6496 C>T in exon 49 of the SPTAN1 gene (NM_001130438.1) The Arg2166Cys missense change 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 or among the various ethnic groups studied in the 1000 Genomes Project, indicating it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a positively charged Arginine residue is replaced by an uncharged Cysteine residue and the gain of a Cysteine may disrupt disulfide bond formation in the alpha-II spectrin protein. Arg2166Cys alters a position in the 22nd spectrin repeat of the protein that is conserved through mammals but not in all related proteins. However, missense mutations at nearby codons have not been reported in association with epilepsy and multiple in-silico algorithms are not consistent in their predictions of whether Arg2166Cys is damaging to the structure/function of the protein. Therefore, based on the currently available information, it is unclear whether Arg2166Cys is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).