Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Pediatrics, |
RCV001290255 | SCV001478083 | pathogenic | Migraine, familial hemiplegic, 1 | 2021-01-26 | criteria provided, single submitter | clinical testing | This variant is absent in Exome Aggregation Consortium (ExAC) database or Genome Aggregation Database (gnomAD). This variant is predicted be in silico tools: SIFT - deleterious, PolyPhen - Probably Damaging, FATHMM pred - Damaging, MutationTaster - diseases causing. The affected Ser616 residue is fully conserved across the 100 vertebrate species in the UCSC Genome Browser. The parents were tested - not detected. |
| Labcorp Genetics |
RCV001863157 | SCV002289807 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2023-04-24 | 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. This variant disrupts the p.Ser616 amino acid residue in CACNA1A. Other variant(s) that disrupt this residue have been observed in individuals with CACNA1A-related conditions (PMID: 34102571, 35722745), which suggests that this may be a clinically significant amino acid residue. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1A protein function. ClinVar contains an entry for this variant (Variation ID: 995995). This variant is also known as c.1843A>C (p.Ser615Arg). This missense change has been observed in individual(s) with clinical features of CACNA1A-related condition (PMID: 35722745). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 616 of the CACNA1A protein (p.Ser616Arg). |
| Wendy Chung Laboratory, |
RCV002227266 | SCV002506543 | 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 |