Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center For Human Genetics And Laboratory Diagnostics, |
RCV000678985 | SCV000805201 | pathogenic | Cerebellar ataxia | 2018-05-11 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000703765 | SCV000832681 | pathogenic | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2022-11-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 560724). This premature translational stop signal has been observed in individual(s) with episodic ataxia 2 (PMID: 27066515). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr1853*) in the CACNA1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1A are known to be pathogenic (PMID: 10371528, 19486177, 25735478, 27250579). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509507 | SCV002819514 | likely pathogenic | Developmental and epileptic encephalopathy, 42 | 2022-12-13 | criteria provided, single submitter | clinical testing | Variant summary: CACNA1A c.5559_5560delCA (p.Tyr1853X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.6202C>T [p.Arg2068Ter], c.6397C>T [p.Arg2133Ter]). The variant was absent in 237970 control chromosomes (gnomAD). c.5559_5560delCA has been reported in the literature in individuals affected with Epilepsy (Truty_2019). This report does not provide unequivocal conclusions about association of the variant with Epileptic Encephalopathy, Early Infantile, 42. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Gene |
RCV003232071 | SCV003929648 | pathogenic | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | Reported as heterozygous in one patient from a cohort of individuals with epilepsy (Truty et al., 2019); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31440721) |