Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000503692 | SCV000595824 | pathogenic | Congenital amegakaryocytic thrombocytopenia | 2017-04-18 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000503692 | SCV000698584 | pathogenic | Congenital amegakaryocytic thrombocytopenia | 2017-01-12 | criteria provided, single submitter | clinical testing | Variant summary: The MPL c.235_236delCT (p.Leu79Glufs) variant results in a premature termination codon, predicted to cause a truncated or absent MPL protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 6/121376 control chromosomes at a frequency of 0.0000494, which does not exceed the estimated maximal expected allele frequency of a pathogenic MPL variant (0.002357). The variant has been reported in affected individuals in the literature in the homozygous and compound heterozygous state. Taken together, this variant is classified as pathogenic. |
Invitae | RCV000818190 | SCV000958789 | pathogenic | Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu79Glufs*84) in the MPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPL are known to be pathogenic (PMID: 8073287, 11133753). This variant is present in population databases (rs587778514, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with congenital amegakaryocytic thrombocytopenia (PMID: 11133753, 17666371). This variant is also known as del235/236. ClinVar contains an entry for this variant (Variation ID: 134822). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002281948 | SCV002571542 | pathogenic | not provided | 2022-09-04 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Published functional studies demonstrate a damaging effect of no protein expression (Gandhi et al., 2005); This variant is associated with the following publications: (PMID: 19388932, 17666371, 21228398, 16470591, 19302922, 31350202, 29625052, 34426522, 31589614, 11133753, 16219544) |
Fulgent Genetics, |
RCV002498569 | SCV002810459 | pathogenic | Congenital amegakaryocytic thrombocytopenia; Primary myelofibrosis; Thrombocythemia 2 | 2022-05-02 | criteria provided, single submitter | clinical testing | |
Neuberg Centre For Genomic Medicine, |
RCV000503692 | SCV004047070 | pathogenic | Congenital amegakaryocytic thrombocytopenia | criteria provided, single submitter | clinical testing | The MPL c.235_236del (p.Leu79GlufsTer84) variant has been reported in homozygous state in individuals affected with Amegakaryocytic Thrombocytopenia, Congenital (Ballmaier M et al.). Experimental studies have shown that this frameshift predicted to result in a complete absence of functional c-Mpl protein. This variant has also been reported to lead to a complete loss of a functional TPO receptor c-Mpl (Ballmaier M et al.). This variant has been submitted with the allele frequency 0.005% in the gnomAD and novel in 1000 genome database. It has been submitted to ClinVar as Pathogenic. This variant causes a frameshift starting with codon Leucine 79, changes this amino acid to Glutamic Acid residue, and creates a premature Stop codon at position 84 of the new reading frame, denoted p.Leu79GlufsTer84. Loss-of-function variants in MPL are known to be pathogenic (Gurney AL et al.) For these reasons, this variant has been classified as Pathogenic. | |
ITMI | RCV000121536 | SCV000085730 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Natera, |
RCV000503692 | SCV001453969 | pathogenic | Congenital amegakaryocytic thrombocytopenia | 2020-09-16 | no assertion criteria provided | clinical testing |