Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025716 | SCV001187960 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-30 | criteria provided, single submitter | clinical testing | The p.R228Q variant (also known as c.683G>A), located in coding exon 6 of the PRKAR1A gene, results from a G to A substitution at nucleotide position 683. The arginine at codon 228 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001066088 | SCV001231083 | uncertain significance | Carney complex, type 1 | 2019-12-03 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PRKAR1A-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces arginine with glutamine at codon 228 of the PRKAR1A protein (p.Arg228Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. |