Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588534 | SCV000697545 | uncertain significance | not provided | 2016-03-07 | criteria provided, single submitter | clinical testing | Variant summary: CACNA1C c.2579G>C affects a conserved nucleotide, resulting in amino acid change from Arg to Pro. 3/4 in-silico tools predict this variant to be damaging (SNPs&GO not captured due to low reliability index). Another variant at this codon c.2579G>A (p.Arg860Gln) is classified as likely pathogenic in ClinVar and has been reported in the literature. However, the variant of interest has not been reported in affected individuals via publications and/or reputable databases; nor evaluated for functional impact by in vivo/vitro studies. Additionally, this variant was not found in 116972 control chromosomes. One clinical lab via ClinVar classified this variant as VUS, without evidence to independently evaluate. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available. |
| Center For Human Genetics And Laboratory Diagnostics, |
RCV000678964 | SCV000805180 | likely pathogenic | Timothy syndrome | 2018-05-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000157123 | SCV001384539 | uncertain significance | Long QT syndrome | 2019-08-24 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Arg860 amino acid residue in CACNA1C. Other variant(s) that disrupt this residue have been observed in individuals with CACNA1C-related conditions (PMID: 25633834, 28600387), which suggests that this may be a clinically significant amino acid residue. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in an individual with clinical features of long QT syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 180284). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 860 of the CACNA1C protein (p.Arg860Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. |
| Blueprint Genetics | RCV000157123 | SCV000206846 | uncertain significance | Long QT syndrome | 2014-08-04 | no assertion criteria provided | clinical testing |