Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Dept. |
RCV003154845 | SCV003843866 | likely pathogenic | Congenital amegakaryocytic thrombocytopenia | criteria provided, single submitter | clinical testing | ||
Neuberg Centre For Genomic Medicine, |
RCV004771539 | SCV005382349 | uncertain significance | Congenital amegakaryocytic thrombocytopenia 1 | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed missense c.1589C>T (p.Pro530Leu) variant in MPL gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Pro530Leu variant is present with allele frequency of 0.0008% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic. Multiple lines of computational evidence (Polyphen - Probably Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The reference amino acid of p.Pro530Leu in MPL is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Pro at position 530 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. However, additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). |