ClinVar Miner

Submissions for variant NM_001205293.3(CACNA1E):c.1696T>C (p.Phe566Leu)

gnomAD frequency: 0.00001  dbSNP: rs377297262
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001591638 SCV001815652 uncertain significance Developmental and epileptic encephalopathy, 69 2020-09-23 criteria provided, single submitter clinical testing The heterozygous c.1696T>C (p.Phe566Leu) variant identified has not been reported in affected individuals in the literature. The variant has 0.00001314 allele frequency in the gnomAD(v3) database (2 out of 152,186 heterozygous alleles) indicating it is an extremely rare allele in the populations represented in this database. The variant affects an evolutionarily conserved reside and is predicted deleterious by in silico prediction tools (CADD score = 27.6, REVEL score = 0.894). Based on the available evidence, the c.1696T>C (p.Phe566Leu) variant in the CACNA1E gene is assessed as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001866140 SCV002260125 uncertain significance not provided 2024-02-17 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 566 of the CACNA1E protein (p.Phe566Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CACNA1E-related conditions. ClinVar contains an entry for this variant (Variation ID: 1213689). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1E protein function. 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.
Genome-Nilou Lab RCV001591638 SCV004179591 uncertain significance Developmental and epileptic encephalopathy, 69 2023-04-11 criteria provided, single submitter clinical testing

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