Submissions for variant NM_001127222.2(CACNA1A):c.1883C>T (p.Ala628Val)

dbSNP: rs1600292507

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000793441	SCV000932793	uncertain significance	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2020-05-04	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of CACNA1A-related conditions (PMID: 32238909). It is also known as p.Ala628Val in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 629 of the CACNA1A protein (p.Ala629Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine.
Cavalleri Lab, Royal College of Surgeons in Ireland	RCV001031011	SCV001160804	likely pathogenic	Developmental and epileptic encephalopathy, 42	2019-12-11	criteria provided, single submitter	research	ACMG evidence PS2, PM2, PP2, PP3