Submissions for variant NM_005373.3(MPL):c.391G>C (p.Gly131Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV004771730	SCV005382447	likely pathogenic	Congenital amegakaryocytic thrombocytopenia 1	2023-05-20	criteria provided, single submitter	clinical testing	The observed missense c.391G>C(p.Gly131Arg) variant in MPL gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Gly131Arg variant has been reported with allele frequency of 0.0004% in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidences (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 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 131 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. This missense variant lies in the splice region and SpliceAI predicts this variant to cause splice donor loss (0.63) and donor gain (0.32). However, additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic.