Submissions for variant NM_001127222.2(CACNA1A):c.4028C>T (p.Ser1343Phe)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002912874	SCV003247961	uncertain significance	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2021-12-12	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 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 serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1344 of the CACNA1A protein (p.Ser1344Phe).
Athena Diagnostics	RCV003482424	SCV004229459	uncertain significance	not provided	2023-08-01	criteria provided, single submitter	clinical testing	Available data are insufficient to determine the clinical significance of the variant at this time. This variant has not been reported in large, multi-ethnic general populations. (http://gnomad.broadinstitute.org) The variant is located in a region that is considered important for protein function and/or structure. Computational tools predict that this variant is damaging.