Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004771709 | SCV005382399 | likely pathogenic | Pyruvate kinase deficiency of red cells | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed missense variant c.958G>A(p.Val320Met) in PKLR gene has been reported previously in compound heterozygous state in an individual with Red cell pyruvate kinase deficiency (Fermo E, et al., 2005). Another missense variant c.958G>C, p.Val320Leu reported to be disease causing (van Wijk R, et al., 2009). The c.958G>A variant is absent in gnomAD Exomes. The amino acid Valine at position 320 is changed to a Methionine changing protein sequence and it might alter its composition and physico-chemical properties. Computational evidence (Polyphen-probabaly damaging, SIFT-tolerated and Mutation Taster-disease causing) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid p.Val320Met in PKLR is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. |