Submissions for variant NM_021098.3(CACNA1H):c.6630_6639dup (p.Thr2214fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003792348	SCV004588639	uncertain significance	Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV	2022-10-28	criteria provided, single submitter	clinical testing	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 has not been reported in the literature in individuals affected with CACNA1H-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr2214Glyfs*14) in the CACNA1H gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 140 amino acid(s) of the CACNA1H protein.
PreventionGenetics, part of Exact Sciences	RCV004539142	SCV004717336	uncertain significance	CACNA1H-related disorder	2024-01-02	no assertion criteria provided	clinical testing	The CACNA1H c.6630_6639dup10 variant is predicted to result in a frameshift and premature protein termination (p.Thr2214Glyfs*14). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Loss of function has not been conclusively established as a mechanism for CACNA1H-related disorders. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.