Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000272977 | SCV000329501 | pathogenic | not provided | 2020-09-01 | criteria provided, single submitter | clinical testing | Nonsense 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 (dramatically reduced levels of expression and abnormal subcellular protein localization) (Cretien et al., 2008); This variant is associated with the following publications: (PMID: 9988267, 18768533, 10598818, 25525159) |
Revvity Omics, |
RCV000033182 | SCV002019902 | pathogenic | Diamond-Blackfan anemia 1 | 2020-08-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002433445 | SCV002747616 | pathogenic | Diamond-Blackfan anemia | 2014-12-19 | criteria provided, single submitter | clinical testing | The p.R94* pathogenic mutation (also known as c.280C>T), located in coding exon 3 of the RPS19 gene, results from a C to T substitution at nucleotide position 280. This changes the amino acid from an arginine to a stop codon within coding exon 3. This pathogenic mutation was first reported in two sisters with Diamond Blackfan anemia, as well as their unaffected mother; one sister had thumb malformations and a duplicated ureter and the other sister had congenital glaucoma, while the mother hand normal hemoglobin levels and no apparent malformations (Draptchinskaia N et al. Nat Genet. 1999; 21(2):169-75). An in vitro functional study found that cells with this pathogenic mutation resulted in a dramatic reduction of expression and a failure of nucleolar localization of the RPS19 protein (Crétien A et al. Haematologica. 2008; 93(11):1627-34). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
OMIM | RCV000033182 | SCV000057018 | pathogenic | Diamond-Blackfan anemia 1 | 1999-02-01 | no assertion criteria provided | literature only |