ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.556C>G (p.Gln186Glu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002909119 SCV003254089 uncertain significance Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2022-07-23 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 186 of the MPL protein (p.Gln186Glu). This variant is present in population databases (rs121913610, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MPL-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
PreventionGenetics, part of Exact Sciences RCV004536446 SCV004120788 uncertain significance MPL-related disorder 2023-06-19 criteria provided, single submitter clinical testing The MPL c.556C>G variant is predicted to result in the amino acid substitution p.Gln186Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-43805106-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004066176 SCV004994759 uncertain significance Inborn genetic diseases 2024-01-16 criteria provided, single submitter clinical testing The c.556C>G (p.Q186E) alteration is located in exon 4 (coding exon 4) of the MPL gene. This alteration results from a C to G substitution at nucleotide position 556, causing the glutamine (Q) at amino acid position 186 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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