Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002435862 | SCV002753380 | likely pathogenic | Diamond-Blackfan anemia | 2019-07-11 | criteria provided, single submitter | clinical testing | The p.R101C variant (also known as c.301C>T), located in coding exon 3 of the RPS19 gene, results from a C to T substitution at nucleotide position 301. The arginine at codon 101 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was identified in an individual with Diamond-Blackfan anemia (DBA) who was responsive to steroid treatment (Boria I et al. Hum. Mutat., 2010 Dec;31:1269-79). A disease-causing mutation, p.R101H, has been described in the same codon in individuals with DBA (Willig TN et al. Blood, 1999 Dec;94:4294-306). Based on data from gnomAD, the T allele has an overall frequency of approximately <0.01% (1/250442). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis.Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV002435862 | SCV004298396 | uncertain significance | Diamond-Blackfan anemia | 2023-07-27 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs782627671, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 101 of the RPS19 protein (p.Arg101Cys). This missense change has been observed in individual(s) with Diamond-Blackfan anemia (PMID: 20960466). ClinVar contains an entry for this variant (Variation ID: 1798891). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This variant disrupts the p.Arg101 amino acid residue in RPS19. Other variant(s) that disrupt this residue have been observed in individuals with RPS19-related conditions (PMID: 27329125), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |