Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004764884 | SCV005374816 | uncertain significance | Neurodevelopmental disorder with speech impairment and with or without seizures | criteria provided, single submitter | clinical testing | The observed missense c.1322A>T (p.Tyr441Phe) variant in CACNA1I gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Tyr441Phe variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Computational evidence (Polyphen - Probably Damaging, SIFT - Damaging and MutationTaster - Polymorphism) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Tyr441Phe in CACNA1I is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Tyr at position 441 is changed to a Phe changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). |