ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1367G>C (p.Arg456Pro)

gnomAD frequency: 0.00001  dbSNP: rs1207248925
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001903410 SCV002171535 uncertain significance Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2024-02-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 456 of the MPL protein (p.Arg456Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1404801). 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. 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 RCV004728923 SCV005337483 uncertain significance MPL-related disorder 2024-03-27 no assertion criteria provided clinical testing The MPL c.1367G>C variant is predicted to result in the amino acid substitution p.Arg456Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0040% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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