ClinVar Miner

Submissions for variant NM_021098.3(CACNA1H):c.2071G>A (p.Gly691Ser)

gnomAD frequency: 0.00002  dbSNP: rs377664706
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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 (formerly Invitae), Labcorp RCV001056800 SCV001221264 likely benign Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV 2023-07-07 criteria provided, single submitter clinical testing
Fulgent Genetics, 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, LabCorp 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.

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