ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.517C>G (p.Pro173Ala)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002886161 SCV003245625 uncertain significance Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 173 of the MPL protein (p.Pro173Ala). This variant is present in population databases (rs202137992, gnomAD 0.009%). 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: 2039970). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MPL protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002886162 SCV003738943 uncertain significance Inborn genetic diseases 2022-12-19 criteria provided, single submitter clinical testing The c.517C>G (p.P173A) 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 517, causing the proline (P) at amino acid position 173 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003228099 SCV003924658 uncertain significance not provided 2022-11-10 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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