Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000778242 | SCV000914410 | uncertain significance | MPL-related disorder | 2018-10-23 | criteria provided, single submitter | clinical testing | The MPL c.1774C>T (p.Arg592Ter) variant is a missense variant. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Control data are unavailable for this variant, which is reported at a frequency of 0.000162 in the South Asian population of the Genome Aggregation Database. This variant occurs in the last exon and may escape nonsense-mediated decay. Based on the limited evidence, the p.Arg592Ter variant is classified as a variant of uncertain significance but suspicious for pathogenicity for MPL-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV002536728 | SCV003247682 | pathogenic | Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia | 2023-11-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg592*) in the MPL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the MPL protein. This variant is present in population databases (rs755447085, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with clinical features of MPL-related conditions (PMID: 35776903). ClinVar contains an entry for this variant (Variation ID: 631607). This variant disrupts a region of the MPL protein in which other variant(s) (p.Pro635Leu) have been determined to be pathogenic (PMID: 10971406, 11071383, 18422784). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |