ClinVar Miner

Submissions for variant NM_021098.3(CACNA1H):c.2990C>T (p.Ala997Val)

gnomAD frequency: 0.00004  dbSNP: rs375023370
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001242806 SCV001415918 uncertain significance Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV 2022-07-05 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 967807). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. This variant is present in population databases (rs375023370, gnomAD 0.008%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 997 of the CACNA1H protein (p.Ala997Val).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002469361 SCV002766435 uncertain significance not specified 2022-11-30 criteria provided, single submitter clinical testing Variant summary: CACNA1H c.2990C>T (p.Ala997Val) results in a non-conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 247532 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2990C>T in individuals affected with Idiopathic Generalized Epilepsy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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