Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002233559 | SCV000820960 | uncertain significance | Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia | 2018-05-29 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with MPL-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with cysteine at codon 491 of the MPL protein (p.Trp491Cys). The tryptophan residue is weakly conserved and there is a large physicochemical difference between tryptophan and cysteine. |