Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000617693 | SCV006065277 | uncertain significance | Cardiovascular phenotype | 2025-04-09 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000357942 | SCV003830325 | uncertain significance | not provided | 2024-01-09 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000357942 | SCV002047841 | uncertain significance | not provided | 2021-01-15 | criteria provided, single submitter | clinical testing | The CACNA1C c.6272A>G; p.Asn2091Ser variant (rs201090446) is reported in the literature in an individual with sudden unexpected death and a history of syncope (Sutphin 2016). This variant is found in the general population with an overall allele frequency of 0.05% (129/263770 alleles) in the Genome Aggregation Database. The asparagine at codon 2091 is moderately conserved, and computational analyses predict that this variant is neutral (REVEL: 0.139). However, functional studies of the variant protein indicate altered electrophysiological properties, including increased current density compared to wildtype protein (Sutphin 2016). Due to limited information, the clinical significance of the p.Asn2091Ser variant is uncertain at this time. References: Sutphin et al. Molecular and Functional Characterization of Rare CACNA1C Variants in Sudden Unexplained Death in the Young. Congenit Heart Dis. 2016 Dec;11(6):683-692. |
| Ce |
RCV000357942 | SCV001148544 | benign | not provided | 2024-05-01 | criteria provided, single submitter | clinical testing | CACNA1C: BP4, BS1, BS2 |
| Ambry Genetics | RCV000617693 | SCV000737727 | likely benign | Cardiovascular phenotype | 2020-12-30 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Center For Human Genetics And Laboratory Diagnostics, |
RCV000519629 | SCV000616620 | uncertain significance | Timothy syndrome | 2017-04-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000357942 | SCV000329185 | uncertain significance | not provided | 2024-10-11 | criteria provided, single submitter | clinical testing | Published functional studies suggest a gain of function effect (PMID: 27218670); 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: 25633834, 24690944, 27218670, 34426522, 30172029, 31737537, 30027834, 24440382) |
| Labcorp Genetics |
RCV001084051 | SCV000254657 | likely benign | Long QT syndrome | 2025-01-30 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003955212 | SCV004774382 | likely benign | CACNA1C-related disorder | 2021-10-28 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
| Clinical Molecular Genetics Laboratory, |
RCV001842950 | SCV000804961 | uncertain significance | Cardiac arrhythmia | 2016-08-18 | no assertion criteria provided | clinical testing |