Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV003448861 | SCV004176662 | likely pathogenic | Classic homocystinuria | 2023-02-14 | criteria provided, single submitter | clinical testing | The missense variant c.1036T>C (p.Cys346Arg) which is located in a mutational hot spot in the CBS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Cysteine at position 346 is changed to an Arginine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted as damaging by SIFT. The amino acid change p.Cys346Arg in CBS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. |