Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000632780 | SCV000753966 | uncertain significance | Noonan syndrome | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 124 of the RRAS protein (p.Thr124Met). This variant is present in population databases (rs369508242, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with RRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 527793). 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 disruptive. 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. |
| Ambry Genetics | RCV002343224 | SCV002623127 | uncertain significance | Inborn genetic diseases | 2022-01-12 | criteria provided, single submitter | clinical testing | The p.T124M variant (also known as c.371C>T), located in coding exon 4 of the RRAS gene, results from a C to T substitution at nucleotide position 371. The threonine at codon 124 is replaced by methionine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |