ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.3085A>G (p.Ile1029Val)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetics and Molecular Pathology, SA Pathology RCV003447775 SCV004175517 likely pathogenic Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures 2023-06-20 criteria provided, single submitter clinical testing The CACNA1C c.3085A>G variant is classified as a LIKELY PATHOGENIC variant (PS2, PM2, PP3) This variant is a single nucleotide change in exon 24/47 of the CACNA1C gene, which is predicted to change the amino acid isoleucine at position 1029 in the protein to valine. The patient is de novo for this variant (PS2). This variant is not in dbSNP and is absent from population databases (PM2). The variant has not been reported in ClinVar or HGMD disease databases. Computational predictions support a deleterious effect on the gene or gene product (PP3). Clinical review is recommended.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn RCV003492878 SCV004239228 likely pathogenic Timothy syndrome; Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures 2023-11-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005100103 SCV005727386 uncertain significance Long QT syndrome 2024-03-25 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 1029 of the CACNA1C protein (p.Ile1029Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 2664800). 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 CACNA1C protein function with a positive 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.

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