Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000170842 | SCV000223397 | uncertain significance | not provided | 2016-11-02 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CACNA1C gene. The I1074V variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the Exome Aggregation Consortium (ExAC) data set, indicating it is not a common benign variant in these populations. Nevertheless, the I1074V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Although this substitution occurs at a position that is conserved across species, V1074 is tolerated in at least one species. Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. This result cannot be interpreted for diagnosis or used for family member screening at this time. |
Invitae | RCV001337841 | SCV001531457 | likely benign | Long QT syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002444686 | SCV002611848 | uncertain significance | Cardiovascular phenotype | 2023-03-06 | criteria provided, single submitter | clinical testing | The p.I1074V variant (also known as c.3220A>G), located in coding exon 26 of the CACNA1C gene, results from an A to G substitution at nucleotide position 3220. The isoleucine at codon 1074 is replaced by valine, an amino acid with highly similar properties. This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |