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 2017-06-16 criteria provided, single submitter clinical testing The P106L variant in the MPL gene has been reported previously in the homozygous state in patients of Qatari and Arab origins in association with thrombocythemia, severe thrombocytosis, and familial thrombosis (Stockklausner et al., 2012; El-Harith et al., 2009). It was also observed in carriers with mild thrombocytosis (El-Harith et al., 2009). This variant is predicted to result in abnormal subcellular distribution of receptors and impaired glycosylation (Stockklausner et al, 2012). Based on the currently available evidence, we interpret P106L variant to be likely pathogenic.
Invitae RCV000814672 SCV000955091 pathogenic Congenital amegakaryocytic thrombocytopenia; essential thrombocytemia 2019-10-29 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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