Submissions for variant NM_001127222.2(CACNA1A):c.1839C>G (p.Ile613Met)

dbSNP: rs374686479

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000853265	SCV000996094	likely pathogenic	Episodic ataxia type 2	2017-12-29	criteria provided, single submitter	clinical testing	This variant has not been previously reported in the literature to our knowledge. The c.1839C>G (p.Ile613Met) variant is absent from population databases, thus is presumed to be rare. This variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the combined evidence, the c.1839C>G (p.Ile613Met) variant is classified as likely pathogenic.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224808	SCV003920899	likely pathogenic	Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42	2021-03-30	criteria provided, single submitter	clinical testing	CACNA1A NM_001127221.1 exon 14 p.Ile614Met (c.1842C>G): This variant has not been reported in the literature, but has been identified as de novo by our laboratory in 1 individual with epilepsy. This variant is not present in large control databases. Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant classified as likely pathogenic.