Submissions for variant NM_021098.3(CACNA1H):c.4777+1G>T

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002871289	SCV003230326	uncertain significance	Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV	2022-08-22	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 affects a donor splice site in intron 26 of the CACNA1H gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CACNA1H cause disease.
GeneDx	RCV004774749	SCV005386698	uncertain significance	not provided	2024-01-17	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge