ClinVar Miner

Submissions for variant NM_001127221.2(CACNA1A):c.5575A>G (p.Ile1859Val)

dbSNP: rs1432354078
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000818027 SCV000958619 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1859 of the CACNA1A protein (p.Ile1859Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant cerebellar ataxia (PMID: 28444220). ClinVar contains an entry for this variant (Variation ID: 660761). 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 with a negative predictive value of 95%. 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.
GeneDx RCV002269319 SCV002553128 uncertain significance not provided 2022-01-20 criteria provided, single submitter clinical testing Identified in a patient with spastic paraplegia and ataxia in published literature, however, no segregation information was provided (Coutelier et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28444220)

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