Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000426548 | SCV000524364 | uncertain significance | not provided | 2016-02-16 | criteria provided, single submitter | clinical testing | The G691S variant in the CACNA1H gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed at any significant frequency in approximately 6100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G691S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties; however, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret G691S as a variant of uncertain significance. |
Labcorp Genetics |
RCV001056800 | SCV001221264 | likely benign | Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002480302 | SCV002786411 | uncertain significance | Epilepsy, childhood absence, susceptibility to, 6; Hyperaldosteronism, familial, type IV | 2022-04-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387842 | SCV004099729 | uncertain significance | not specified | 2023-09-11 | criteria provided, single submitter | clinical testing | Variant summary: CACNA1H c.2071G>A (p.Gly691Ser) 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 2.1e-05 in 232710 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2071G>A in individuals affected with Idiopathic Generalized Epilepsy and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |