Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000697539 | SCV000826158 | uncertain significance | Noonan syndrome | 2018-06-14 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RRAS-related disease. This variant is present in population databases (rs775437600, ExAC 0.002%). This sequence change replaces aspartic acid with histidine at codon 59 of the RRAS protein (p.Asp59His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. |
| Ambry Genetics | RCV003380686 | SCV004088628 | uncertain significance | Inborn genetic diseases | 2023-06-29 | criteria provided, single submitter | clinical testing | The p.D59H variant (also known as c.175G>C), located in coding exon 2 of the RRAS gene, results from a G to C substitution at nucleotide position 175. The aspartic acid at codon 59 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |