Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Pittsburgh Clinical Genomics Laboratory, |
RCV004785168 | SCV005397752 | likely pathogenic | Spinocerebellar ataxia type 6 | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence variant is a two-nucleotide deletion (delTT) in exon 36 of 47 of the CACNA1A gene and results in an early termination signal 9 amino acids downstream of the frameshift at the Phe1805 codon. This variant is predicted to generate a non-functional allele through either the expression of a truncated protein or a loss of calcium voltage-gated channel subunit alpha1 A expression due to nonsense mediated decay. This variant is absent from ClinVar and has not been observed in an individual affected by a CACNA1A-related disorder in the published literature, to our knowledge. This variant is present in the from the gnomAD v4.0.0 population database (1 of 833,090 alleles, 0.0001%). Studies examining the functional consequence of this variant have not been published, to our knowledge. Haploinsufficiency in CACNA1A is a known mechanism of disease (PMID: 33737904). Based upon the evidence, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PVS1 |