Submissions for variant NM_001127222.2(CACNA1A):c.6703C>T (p.His2235Tyr)

dbSNP: rs903913051

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001968557	SCV002246296	uncertain significance	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2020-12-21	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 with CACNA1A-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces histidine with tyrosine at codon 2236 of the CACNA1A protein (p.His2236Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine.