Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523450 | SCV000616669 | pathogenic | not provided | 2022-05-19 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24091540, 26863999, 31618753) |
| Athena Diagnostics | RCV000523450 | SCV000841274 | pathogenic | not provided | 2021-04-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been confirmed to occur de novo in multiple individuals with clinical features associated with this gene. Computational tools predict that this variant is damaging. |
| ARUP Laboratories, |
RCV000523450 | SCV001473890 | likely pathogenic | not provided | 2020-01-22 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics Laboratory, |
RCV001252961 | SCV001427033 | likely pathogenic | CACNA1A-associated disorders | 2019-05-24 | no assertion criteria provided | clinical testing | The p.Arg1359Trp variant in the CACNA1A gene has been previously reported de novo in two unrelated individuals, one individual with early onset epilepsy, ataxia, dysmetria, oculomotor apraxia, tremor, developmental delay, intellectual disability, speech delay, hypotonia, and pyramidal sign (Ohba et al., 2013), and one individual with an undescribed neurological condition (Nolan and Carlson, 2015). This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The CACNA1A gene has fewer missense variants in the general population than expected. A low rate of missense variation may suggest that this gene is intolerant to missense variation. Computational tools predict that the p.Arg1359Trp variant is deleterious; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Arg1359Trp variant as likely pathogenic for CACNA1A-assocatied disorders in an autosomal dominant manner based on the information above. [ACMG evidence codes used: PS2; PM2; PP2; PP3] |
| Génétique des Maladies du Développement, |
RCV001787103 | SCV002029085 | pathogenic | Delayed gross motor development | no assertion criteria provided | clinical testing |