Submissions for variant NM_001127222.2(CACNA1A):c.6697C>T (p.Pro2233Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003985620	SCV004119218	uncertain significance	CACNA1A-related disorder	2022-11-07	criteria provided, single submitter	clinical testing	The CACNA1A c.6697C>T variant is predicted to result in the amino acid substitution p.Pro2233Ser. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003778328	SCV004571084	uncertain significance	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2023-08-14	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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2234 of the CACNA1A protein (p.Pro2234Ser).