Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002627689 | SCV002976929 | uncertain significance | Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia | 2022-09-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 321 of the MPL protein (p.Arg321Trp). This variant is present in population databases (rs566429212, gnomAD 0.02%). This missense change has been observed in individual(s) with essential thrombocytopenia (PMID: 26423830). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |