Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000798314 | SCV000937922 | pathogenic | Congenital amegakaryocytic thrombocytopenia; essential thrombocytemia | 2019-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 102 of the MPL protein (p.Arg102Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs763568293, ExAC 0.001%). This variant has been observed in individuals affected with congenital amegakaryocytic thrombocytopenia (PMID: 16470591, 21659346). This variant has been reported to affect MPL protein function (PMID: 24438083). This variant disrupts the p.Arg102 amino acid residue in MPL. Other variant(s) that disrupt this residue have been observed in individuals with MPL-related conditions (PMID: 10971406, 11972523, 16470591), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
Natera, |
RCV001272212 | SCV001453971 | pathogenic | Congenital amegakaryocytic thrombocytopenia | 2020-09-16 | no assertion criteria provided | clinical testing |