Submissions for variant NM_001127222.2(CACNA1A):c.6346T>G (p.Ser2116Ala)

gnomAD frequency: 0.00002  dbSNP: rs576057388

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520739	SCV000621495	uncertain significance	not provided	2017-10-12	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the CACNA1A gene. The S2117A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The S2117A variant is a non-conservative amino acid substitution, which is likely toimpact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Serine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently availableinformation, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV001070996	SCV001236276	likely benign	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2023-11-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000520739	SCV001334849	uncertain significance	not provided	2020-02-01	criteria provided, single submitter	clinical testing