Total submissions: 28
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Human Genome Sequencing Center Clinical Lab, |
RCV000015769 | SCV000839961 | pathogenic | Acquired polycythemia vera | 2018-02-08 | criteria provided, single submitter | clinical testing | The c.1849G>T (p.V617F) variant in the JAK2 gene is commonly reported as a somatic change in myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, primary myelofibrosis [PMID: 15781101, 15858187, 15837627, 19074595]. Recently, this variant has also been described as one of the most common drivers of age-related clonal hematopoiesis [PMID: 27563148]. The c.1849G>T (p.V617F) variant in the JAK2 gene is classified as a pathogenic somatic variant. |
Fulgent Genetics, |
RCV000763621 | SCV000894475 | pathogenic | Primary familial polycythemia due to EPO receptor mutation; Acquired polycythemia vera; Budd-Chiari syndrome; Primary myelofibrosis; Acute myeloid leukemia; Thrombocythemia 3 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001092995 | SCV001249759 | pathogenic | not provided | 2024-01-01 | criteria provided, single submitter | clinical testing | JAK2: PM1, PM5, PM6, PS4:Moderate, PP4, PS3:Supporting |
Gene |
RCV001092995 | SCV001825403 | pathogenic | not provided | 2023-04-27 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: induces rapid tumorigenesis in mice, and leads to constitutive activation of the JAK2 kinase, excess JAK/STAT signaling, and increased cell survival and proliferation (Kralovics et al., 2005; James et al., 2005; Abe et al., 2009; Kapralova et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23425079, 25698270, 21120162, 21689158, 27777768, 28205126, 24381227, 16755940, 16293597, 29349042, 31721094, 28596259, 29641446, 23300178, 16156870, 16871278, 20182460, 24068492, 15781101, 19287384, 25157968, 24986690, 16081687, 16709929, 18394554, 24404189, 20339092, 22571758, 20631743, 23115274, 22818858, 22041374, 22829971, 22422826, 21160067, 19549988, 16341032, 26228487, 23537216, 23248577, 23057517, 19195039, 17596137, 17440677, 17194663, 16990759, 16904848, 16954506, 16926301, 15920007, 15858187, 15860661, 26556299, 19293426, 16762626, 15793561, 30944118, 33144682, 32581362, 31447099, 19327411) |
Labcorp Genetics |
RCV001092995 | SCV002307245 | likely pathogenic | not provided | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 617 of the JAK2 protein (p.Val617Phe). 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 is a well-known somatic change that has been reported as a recurrent variant in many individuals affected with myeloproliferative disorders (PMID: 15920007, 15781101, 15858187, 15793561, 16603627). ClinVar contains an entry for this variant (Variation ID: 14662). 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) performed at Invitae indicates that this missense variant is not expected to disrupt JAK2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects JAK2 function (PMID: 15793561, 23535062). A different missense substitution at this codon (p.Val617Ile) has been reported to segregate with autosomal dominant hereditary thrombocytosis as a germline change in a single family (PMID: 22397670). Functional studies show that this variant results in constitutive kinase activation and cytokine hyper-responsiveness (PMID: 23535062, 22397670). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Provincial Medical Genetics Program of British Columbia, |
RCV000015769 | SCV002320869 | pathogenic | Acquired polycythemia vera | 2022-01-01 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000015770 | SCV002765070 | pathogenic | Primary myelofibrosis | 2022-11-24 | criteria provided, single submitter | clinical testing | _x000D_ Criteria applied: PS3, PS4, PM1, PM5, PP4 |
Revvity Omics, |
RCV000022627 | SCV003831788 | likely pathogenic | Thrombocythemia 3 | 2022-10-03 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000015770 | SCV003835086 | pathogenic | Primary myelofibrosis | 2021-08-30 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000015769 | SCV004806756 | likely pathogenic | Acquired polycythemia vera | 2024-09-02 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000015769 | SCV000036034 | pathogenic | Acquired polycythemia vera | 2014-08-07 | no assertion criteria provided | literature only | |
OMIM | RCV000015770 | SCV000036036 | pathogenic | Primary myelofibrosis | 2014-08-07 | no assertion criteria provided | literature only | |
OMIM | RCV000015771 | SCV000036037 | pathogenic | Acute myeloid leukemia | 2014-08-07 | no assertion criteria provided | literature only | |
OMIM | RCV000015772 | SCV000036038 | risk factor | Budd-Chiari syndrome, susceptibility to, somatic | 2014-08-07 | no assertion criteria provided | literature only | |
OMIM | RCV000022627 | SCV000043916 | pathogenic | Thrombocythemia 3 | 2014-08-07 | no assertion criteria provided | literature only | |
OMIM | RCV000022628 | SCV000043917 | affects | Primary familial polycythemia due to EPO receptor mutation | 2014-08-07 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420273 | SCV000504652 | not provided | Chronic myelogenous leukemia, BCR-ABL1 positive | 2016-03-10 | no assertion provided | literature only | |
Database of Curated Mutations |
RCV000427081 | SCV000504653 | likely pathogenic | Myeloproliferative disorder | 2016-05-13 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000015770 | SCV000504655 | likely pathogenic | Primary myelofibrosis | 2015-07-14 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000015771 | SCV000504656 | likely pathogenic | Acute myeloid leukemia | 2014-10-02 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428162 | SCV000504657 | not provided | Subacute lymphoid leukemia | 2016-03-10 | no assertion provided | literature only | |
Database of Curated Mutations |
RCV000015769 | SCV000504658 | not provided | Acquired polycythemia vera | 2016-03-10 | no assertion provided | literature only | |
NIHR Bioresource Rare Diseases, |
RCV001003803 | SCV001162249 | likely pathogenic | Primary myelofibrosis; Splenomegaly | no assertion criteria provided | research | ||
NIHR Bioresource Rare Diseases, |
RCV001003804 | SCV001162250 | pathogenic | Polycythemia | no assertion criteria provided | research | ||
NIHR Bioresource Rare Diseases, |
RCV000427081 | SCV001162251 | pathogenic | Myeloproliferative disorder | no assertion criteria provided | research | ||
Laboratory of Diagnostic Genome Analysis, |
RCV001092995 | SCV002036319 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001092995 | SCV002037447 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Molecular Diagnostics Laboratory, |
RCV000015769 | SCV004175181 | pathogenic | Acquired polycythemia vera | no assertion criteria provided | provider interpretation |