ClinVar Miner

Submissions for variant NM_005373.2(MPL):c.317C>T (p.Pro106Leu) (rs750046020)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255329 SCV000321906 likely pathogenic not provided 2021-01-19 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with abnormal subcellular distribution of receptors and impaired glycosylation (Stockklausner et al, 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23351976, 30553997, 31808840, 30183354, 31092065, 30318940, 28408900, 28444727, 28979237, 28955303, 27884173, 28034873, 26077850, 25538044, 19036112, 30996850, 31135094)
Invitae RCV000814672 SCV000955091 pathogenic Congenital amegakaryocytic thrombocytopenia; essential thrombocytemia 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 106 of the MPL protein (p.Pro106Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs750046020, ExAC 0.04%). This variant has been observed to segregate with MPL-related conditions in several families (PMID: 19036112, 25538044). ClinVar contains an entry for this variant (Variation ID: 265248). Experimental studies have shown that this missense change has a deleterious effect on protein function (PMID: 25538044). For these reasons, this variant has been classified as Pathogenic.

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