Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004790141 | SCV005400700 | likely pathogenic | Haim-Munk syndrome | 2023-06-22 | criteria provided, single submitter | clinical testing | The observed missense c.745G>T(p.Val249Phe) variant in CTSC gene has been reported in homozygous or compound heterozygous state in individuals affected with CTSC related disorder (Toomes C, et. al., 1999; Hart PS, et. al., 2000; Selvaraju V, et. al., 2003). The p.Val249Phe variant is absent in gnomAD Exomes database. This variant has not been reported 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 CTSC is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Val at position 249 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 Likely Pathogenic. |