ClinVar Miner

Submissions for variant NM_021098.3(CACNA1H):c.4646T>C (p.Met1549Thr)

gnomAD frequency: 0.00001  dbSNP: rs1195869438
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691639 SCV000819425 uncertain significance Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV 2023-02-02 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with hypertension (Invitae). This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1549 of the CACNA1H protein (p.Met1549Thr). ClinVar contains an entry for this variant (Variation ID: 570710). 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. This variant disrupts the p.Met1549 amino acid residue in CACNA1H. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25907736, 27729216). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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