Submissions for variant NM_001205293.3(CACNA1E):c.4565C>T (p.Ser1522Phe)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003109940	SCV003761737	uncertain significance	not provided	2022-07-25	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Neuberg Centre For Genomic Medicine, NCGM	RCV003340659	SCV004048118	uncertain significance	Developmental and epileptic encephalopathy, 69		criteria provided, single submitter	clinical testing	The missense variant in c.4565C>T (p.Ser1522Phe) in CACNA1E gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ser1522Phe variant is reported with the allele frequency (0.001%) in the gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The amino acid Ser at position 1522 is changed to a Phe changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Ser1522Phe in CACNA1E is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).
Genome-Nilou Lab	RCV003340659	SCV004179660	uncertain significance	Developmental and epileptic encephalopathy, 69	2023-04-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003109940	SCV004665070	benign	not provided	2023-11-28	criteria provided, single submitter	clinical testing