Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004785904 | SCV005401026 | uncertain significance | Renal tubular dysgenesis of genetic origin | 2023-06-22 | criteria provided, single submitter | clinical testing | The observed missense c.1882T>C(p.Trp628Arg) variant in ACE gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Trp628Arg variant is absent in gnomAD Exomes database. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidence (Polyphen - probably Damaging, SIFT -Damaging and MutationTaster -disease causing) predict damaging effect on protein structure and function for this variant. The reference amino acid in ACE is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Trp at position 628 is changed to a Arg 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). In absence of another reportable variant in ACE gene, the molecular diagnosis is not confirmed. |