Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001050559 | SCV001214674 | uncertain significance | Carney complex, type 1 | 2022-03-04 | 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. ClinVar contains an entry for this variant (Variation ID: 847087). This variant has not been reported in the literature in individuals affected with PRKAR1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 113 of the PRKAR1A protein (p.Tyr113Cys). |
| Ambry Genetics | RCV002451205 | SCV002618245 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-22 | criteria provided, single submitter | clinical testing | The p.Y113C variant (also known as c.338A>G), located in coding exon 2 of the PRKAR1A gene, results from an A to G substitution at nucleotide position 338. The tyrosine at codon 113 is replaced by cysteine, an amino acid with highly dissimilar properties. This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). 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. |