Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000691097 | SCV000818840 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2022-03-22 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 570273). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 278 of the CACNA1A protein (p.Ala278Thr). |
| Breda Genetics srl | RCV001174531 | SCV001250740 | likely pathogenic | Developmental and epileptic encephalopathy, 42 | 2020-05-15 | criteria provided, single submitter | clinical testing | We have detected a heterozygous variant in exon 6 of the CACNA1A gene, c.832G>A (p.Ala278Thr), rs1013100046, reference transcript NM_001127221.1. The variant is reported as uncertain for early infantile epileptic encephalopathy-42 and episodic ataxia type 2 in ClinVar (Variation ID: 570273). There is no information on frequency in gnomAD, 1000 Genomes or NHLI Exome Sequencing Project (ESP). The nucleotide position is conserved across 35 mammalian species (GERP RS: 5.27). In silico analysis indicates that the variant might be damaging. |
| Gene |
RCV001731893 | SCV001981920 | uncertain significance | not provided | 2021-09-08 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Athena Diagnostics Inc | RCV001731893 | SCV002770800 | uncertain significance | not provided | 2022-02-16 | criteria provided, single submitter | clinical testing |