Submissions for variant NM_001130438.3(SPTAN1):c.3358G>A (p.Gly1120Arg)

gnomAD frequency: 0.00001  dbSNP: rs748698544

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519099	SCV000617139	uncertain significance	not provided	2015-09-09	criteria provided, single submitter	clinical testing	A variant of unknown significance has been identified in the SPTAN1 gene. The G1120R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant 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 G1120R 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. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, previously reported pathogenic variants in SPTAN1 include in-frame deletions or duplications located within the last four spectrin repeats of the protein, which are essential for dimerization (Saitsu et al., 2010), and the G1120 residue is outside this region. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001731745	SCV001984102	uncertain significance	not specified	2020-09-24	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001809467	SCV002056756	uncertain significance	Developmental and epileptic encephalopathy, 5	2021-07-15	criteria provided, single submitter	clinical testing