Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004727213 | SCV005329639 | uncertain significance | Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits | 2023-05-20 | criteria provided, single submitter | clinical testing | The missense variant c.3086C>T(p.Pro1029Leu) in CACNA1G gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The observed variant has allele frequency of 0.002% in gnomAD exomes database. This variant has not been reported to the ClinVar database. Multiple lines of computational evidence (Polyphen - Benign, SIFT - Tolerated and MutationTaster - disease causing) predict conflicting evidences on protein structure and function for this variant. The amino acidchange p.Pro1029Leu in CACNA1G is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Pro at position 1029 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance (VUS). |