Submissions for variant NM_001127222.2(CACNA1A):c.1785C>G (p.Tyr595Ter)

dbSNP: rs2057948502

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV001288484	SCV001475632	pathogenic	not provided	2020-04-08	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001871718	SCV002179075	pathogenic	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2023-01-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This sequence change creates a premature translational stop signal (p.Tyr596*) in the CACNA1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1A are known to be pathogenic (PMID: 10371528, 19486177, 25735478, 27250579). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 994806).
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV003294188	SCV004009686	likely pathogenic	Episodic ataxia type 2	2022-10-11	criteria provided, single submitter	research