Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001049766 | SCV001213836 | pathogenic | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2022-12-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 8510). This variant is also known as 5404T>C or 5129T>C. This missense change has been observed in individual(s) with familial hemiplegic migraine (PMID: 15240985, 15452324). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. 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 1709 of the CACNA1A protein (p.Ile1709Thr). 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. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001804718 | SCV002050473 | pathogenic | not provided | 2022-03-23 | 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); This variant is associated with the following publications: (PMID: 20837964, 15452324, 28717674, 15240985) |
| Centre de Biologie Pathologie Génétique, |
RCV002273923 | SCV002558939 | pathogenic | Neurodevelopmental delay | criteria provided, single submitter | clinical testing | ||
| Ambry Genetics | RCV002345236 | SCV002645597 | likely pathogenic | Inborn genetic diseases | 2018-05-11 | criteria provided, single submitter | clinical testing | The p.I1709T variant (also known as c.5126T>C), located in coding exon 33 of the CACNA1A gene, results from a T to C substitution at nucleotide position 5126. The isoleucine at codon 1709 is replaced by threonine, an amino acid with similar properties. This variant (designated as I1710T) occurred de novo in a proband with slowly progressive cerebellar ataxia, cerebellar atrophy, and hemiplegic migraine attacks. This proband's two children both have cerebellar ataxia, cerebellar atrophy, migraine without aura, two episodes of hemiplegic migraine, and a history of childhood seizures (Kors EE et al. Neurology, 2004 Sep;63:1136-7). This variant also occurred de novo in a 14-year-old female with right hemiplegia, aphasia, and altered consciousness followed by recurrent and prolonged right unilateral seizures after a head trauma; she had two additional attacks of headaches with comas, hemiplegia, and status epilepticus, moderate ataxia between episodes, a normal brain MRI, and an abnormal EEG (Riant F et al. Neurology, 2010 Sep;75:967-72; Beauvais K et al. Eur. Neurol., 2004 Jul;52:58-61). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| OMIM | RCV000009035 | SCV000029252 | pathogenic | Migraine, familial hemiplegic, 1 | 2004-09-28 | no assertion criteria provided | literature only | |
| OMIM | RCV000009036 | SCV000029253 | pathogenic | Spinocerebellar ataxia type 6 | 2004-09-28 | no assertion criteria provided | literature only | |
| Mendelics | RCV000157056 | SCV000199321 | pathogenic | Episodic ataxia type 2 | 2014-11-24 | no assertion criteria provided | clinical testing |