ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.622C>A (p.Gln208Lys)

gnomAD frequency: 0.00006  dbSNP: rs111460954
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001048802 SCV001212825 uncertain significance Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2022-07-15 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 208 of the MPL protein (p.Gln208Lys). This variant is present in population databases (rs111460954, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MPL-related conditions. ClinVar contains an entry for this variant (Variation ID: 134828). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002483221 SCV002793499 uncertain significance Congenital amegakaryocytic thrombocytopenia; Primary myelofibrosis; Thrombocythemia 2 2021-11-11 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003129780 SCV003808907 uncertain significance not provided 2021-06-16 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004530023 SCV004108679 uncertain significance MPL-related disorder 2023-07-11 criteria provided, single submitter clinical testing The MPL c.622C>A variant is predicted to result in the amino acid substitution p.Gln208Lys. This variant has been reported in an individual with essential thrombocythemia (Rendo et al. 2022. PubMed ID: 35449633). This variant is reported in 0.032% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-43805172-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
ITMI RCV000121543 SCV000085737 not provided not specified 2013-09-19 no assertion provided reference population
Natera, Inc. RCV001831914 SCV002086027 uncertain significance Congenital amegakaryocytic thrombocytopenia 2020-08-20 no assertion criteria provided clinical testing

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