Total submissions: 25
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Rady Children's Institute for Genomic Medicine, |
RCV000853347 | SCV000996209 | pathogenic | Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria | 2018-11-02 | criteria provided, single submitter | clinical testing | This variant has been previously reported as a mosaic change in patients with metaphyseal chondromatosis and elevated D-2-hydroxyglutaric aciduria (PMID: 24049096, 22025298). It is absent from the gnomAD population databases and thus is presumed to be rare. The c.395G>A, p.Arg132H variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. The p.Arg132H variant results in loss of its native enzymatic activity and gain of alternative enzymatic activity (producing D-2-hydroxyglutarate) (PMID 21446021). Structural studies demonstrated that when p.Arg132 is mutated to histidine (R132H), residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG (PMID 19935646). Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumors in patients with inborn errors of 2HG metabolism (PMID 18931888). Based on the available evidence, the c.395G>A, p.Arg132H variant is classified as Pathogenic. |
Clinical Genetics and Genomics, |
RCV001269510 | SCV001449548 | pathogenic | not provided | 2019-10-29 | criteria provided, single submitter | clinical testing | |
Kasturba Medical College, |
RCV002227447 | SCV002507195 | pathogenic | Enchondromatosis | 2022-05-09 | criteria provided, single submitter | clinical testing | |
Baylor- |
RCV002227447 | SCV002764259 | likely pathogenic | Enchondromatosis | criteria provided, single submitter | research | ||
Ce |
RCV001269510 | SCV004011290 | pathogenic | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | IDH1: PS4, PM1, PM2, PP4, PS3:Supporting |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV003387509 | SCV004099007 | pathogenic | Metaphyseal chondromatosis | 2023-08-02 | criteria provided, single submitter | clinical testing | PS4, PM2, PM5, PM6_Strong, PP3 |
OMIM | RCV000144504 | SCV000189823 | pathogenic | Glioblastoma multiforme, somatic | 2014-08-21 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420454 | SCV000503802 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431117 | SCV000503803 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000441845 | SCV000503804 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419255 | SCV000503805 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000429987 | SCV000503806 | pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440637 | SCV000503807 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423408 | SCV000503808 | likely pathogenic | Medulloblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428884 | SCV000503809 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439554 | SCV000503810 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422344 | SCV000503811 | likely pathogenic | Brainstem glioma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433068 | SCV000503812 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442517 | SCV000503813 | likely pathogenic | Astrocytoma | 2015-07-14 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421389 | SCV000503814 | likely pathogenic | Myelodysplastic syndrome | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432047 | SCV000503815 | likely pathogenic | Prostate adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000445280 | SCV000503816 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427239 | SCV000503817 | likely pathogenic | Adenoid cystic carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423229 | SCV000505707 | not provided | Oligodendroglioma | 2016-03-10 | no assertion provided | literature only | |
Genomics England Pilot Project, |
RCV001542733 | SCV001760072 | likely pathogenic | Glioma susceptibility 1 | no assertion criteria provided | clinical testing |