Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV002493820 | SCV002798314 | uncertain significance | Epilepsy, childhood absence, susceptibility to, 6; Hyperaldosteronism, familial, type IV | 2022-02-08 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002547606 | SCV003739023 | uncertain significance | Inborn genetic diseases | 2022-06-28 | criteria provided, single submitter | clinical testing | The c.5083G>A (p.G1695S) alteration is located in exon 29 (coding exon 28) of the CACNA1H gene. This alteration results from a G to A substitution at nucleotide position 5083, causing the glycine (G) at amino acid position 1695 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003771038 | SCV004594871 | uncertain significance | Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV | 2023-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1695 of the CACNA1H protein (p.Gly1695Ser). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CACNA1H protein function. ClinVar contains an entry for this variant (Variation ID: 1049356). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). |
| Department of Pathology and Laboratory Medicine, |
RCV001355362 | SCV001550232 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The CACNA1H p.Gly1689Ser variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs946594196) and in control databases in 3 of 271274 chromosomes at a frequency of 0.00001106 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 3 of 123842 chromosomes (freq: 0.000024), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Gly1689 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |