ClinVar Miner

Submissions for variant NM_021098.3(CACNA1H):c.5521G>A (p.Val1841Met)

gnomAD frequency: 0.00015  dbSNP: rs370975488
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000694963 SCV000823435 uncertain significance Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1841 of the CACNA1H protein (p.Val1841Met). This variant is present in population databases (rs370975488, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. ClinVar contains an entry for this variant (Variation ID: 573317). 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 with a positive predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002493194 SCV002792154 uncertain significance Epilepsy, childhood absence, susceptibility to, 6; Hyperaldosteronism, familial, type IV 2022-02-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV004025224 SCV004914946 uncertain significance Inborn genetic diseases 2024-02-13 criteria provided, single submitter clinical testing The c.5521G>A (p.V1841M) alteration is located in exon 33 (coding exon 32) of the CACNA1H gene. This alteration results from a G to A substitution at nucleotide position 5521, causing the valine (V) at amino acid position 1841 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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