Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000170826 | SCV000223381 | uncertain significance | not provided | 2019-11-15 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 190688; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
| Labcorp Genetics |
RCV000463099 | SCV000553008 | likely benign | Long QT syndrome | 2024-12-22 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002345574 | SCV002646853 | uncertain significance | Cardiovascular phenotype | 2021-06-18 | criteria provided, single submitter | clinical testing | The p.R1780C variant (also known as c.5338C>T), located in coding exon 42 of the CACNA1C gene, results from a C to T substitution at nucleotide position 5338. The arginine at codon 1780 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly 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. |
| Fulgent Genetics, |
RCV002492701 | SCV002781812 | uncertain significance | Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8 | 2022-02-14 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003488417 | SCV004240935 | likely benign | not specified | 2023-12-12 | criteria provided, single submitter | clinical testing | Variant summary: CACNA1C c.5338C>T (p.Arg1780Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.9e-05 in 1612396 control chromosomes, predominantly at a frequency of 0.00017 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 17 fold of the estimated maximal expected allele frequency for a pathogenic variant in CACNA1C causing Timothy Syndrome phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.5338C>T in individuals affected with Timothy Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified as VUS (n=3) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |