Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000631620 | SCV000752702 | benign | Long QT syndrome | 2025-01-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002343206 | SCV002646461 | uncertain significance | Cardiovascular phenotype | 2022-06-14 | criteria provided, single submitter | clinical testing | The p.E1792G variant (also known as c.5375A>G), located in coding exon 42 of the CACNA1C gene, results from an A to G substitution at nucleotide position 5375. The glutamic acid at codon 1792 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002507061 | SCV002815554 | uncertain significance | Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8 | 2021-09-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702215 | SCV005202155 | likely benign | not specified | 2024-07-01 | criteria provided, single submitter | clinical testing | Variant summary: CACNA1C c.5375A>G (p.Glu1792Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.8e-05 in 1606640 control chromosomes. The observed variant frequency is approximately 3.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in CACNA1C causing Timothy Syndrome phenotype (1e-05). c.5375A>G has been reported in the literature in at least one individual with arrhythmia, however these report(s) do not provide unequivocal conclusions about association of the variant with Timothy Syndrome (e.g., Richard_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 30471092). ClinVar contains an entry for this variant (Variation ID: 526952). Based on the evidence outlined above, the variant was classified as likely benign. |