ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.4166T>C (p.Ile1389Thr)

dbSNP: rs2144767456
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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 RCV001882266 SCV002165322 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2021-11-12 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1390 of the CACNA1A protein (p.Ile1390Thr). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. 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. 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.
3billion RCV003314024 SCV004013536 uncertain significance Developmental and epileptic encephalopathy, 42 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.95). Therefore, this variant is classified as Uncertain significance according to the recommendation of ACMG/AMP guideline.

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