Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000599194 | SCV000710323 | likely pathogenic | not provided | 2017-12-27 | criteria provided, single submitter | clinical testing | The c.1589_1590delTT variant in the CACNA1A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1589_1590delT variant causes a frameshift starting with codon Phenylalanine 530, changes this amino acid to a Tyrosine residue, and creates a premature Stop codon at position 25 of the new reading frame, denoted p.Phe530TyrfsX25. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1589_1590delTT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1589_1590delTT as a likely pathogenic variant. |
Clinical Genomics Laboratory, |
RCV003458467 | SCV004177112 | likely pathogenic | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2023-07-26 | criteria provided, single submitter | clinical testing | The CACNA1A c.1586_1587del (p.Phe529fs) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline likely pathogenic variant by one submitter. This variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by deleting two nucleotides, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Additionally, other variants that introduce a premature termination codon in this region have been identified in individuals with CACNA1-related disorders and are considered pathogenic (Damaj L et al., PMID: 25735478; Sintas C et al., PMID: 28566750). Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic. |