Submissions for variant NM_001127222.2(CACNA1A):c.2603C>T (p.Ala868Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002700944	SCV002990914	uncertain significance	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2022-10-03	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1A protein function. This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 869 of the CACNA1A protein (p.Ala869Val).
CeGaT Center for Human Genetics Tuebingen	RCV003312061	SCV004011034	uncertain significance	not provided	2023-08-01	criteria provided, single submitter	clinical testing	CACNA1A: PM2, PP2, PP3