ClinVar Miner

Submissions for variant NM_005373.2(MPL):c.769C>T (p.Arg257Cys) (rs121913611)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001038272 SCV001201736 pathogenic Congenital amegakaryocytic thrombocytopenia; essential thrombocytemia 2019-09-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 257 of the MPL protein (p.Arg257Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs121913611, ExAC 0.02%). This variant has been observed in individual(s) with congenital amegakaryocytic thrombocytopenia (PMID: 28859041, 10971406). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 14156). This variant has been reported to affect MPL protein function (PMID: 18422784, 20188141). This variant disrupts the p.Arg257 amino acid residue in MPL. Other variant(s) that disrupt this residue have been observed in individuals with MPL-related conditions (PMID: 16470591), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000015219 SCV000035477 pathogenic Congenital amegakaryocytic thrombocytopenia 2008-06-01 no assertion criteria provided literature only

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