Submissions for variant NM_001127222.2(CACNA1A):c.2133C>G (p.Ile711Met)

dbSNP: rs764839814

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519829	SCV000618721	pathogenic	not provided	2024-09-18	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 35722745)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001853632	SCV002208573	uncertain significance	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2020-12-30	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 with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 450171). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 712 of the CACNA1A protein (p.Ile712Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine.
Wendy Chung Laboratory, Columbia University Medical Center	RCV002227178	SCV002506539	likely pathogenic	Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 52	2022-03-20	criteria provided, single submitter	clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV003492089	SCV004232712	likely pathogenic	Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42	2023-12-14	criteria provided, single submitter	research