ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1904C>T (p.Pro635Leu)

dbSNP: rs121913612
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001378786 SCV001576440 pathogenic Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2023-11-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 635 of the MPL protein (p.Pro635Leu). This variant is present in population databases (rs121913612, gnomAD 0.0009%). This missense change has been observed in individual(s) with congenital amegakaryocytic thrombocytopenia (PMID: 10971406, 11071383). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 14157). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MPL protein function. Experimental studies have shown that this missense change affects MPL function (PMID: 18422784). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005016267 SCV005650350 likely pathogenic Primary myelofibrosis; Thrombocythemia 2; Congenital amegakaryocytic thrombocytopenia 1 2024-02-09 criteria provided, single submitter clinical testing
OMIM RCV004558257 SCV000035478 pathogenic Congenital amegakaryocytic thrombocytopenia 1 2008-06-01 no assertion criteria provided literature only
Natera, Inc. RCV000015220 SCV002089522 likely pathogenic Congenital amegakaryocytic thrombocytopenia 2020-06-26 no assertion criteria provided clinical testing

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