ClinVar Miner

Submissions for variant NM_001022.4(RPS19):c.280C>T (p.Arg94Ter)

dbSNP: rs61762293
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, Revvity 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

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