Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023706 | SCV001185621 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-10 | criteria provided, single submitter | clinical testing | The p.E17D variant (also known as c.51A>T), located in coding exon 1 of the PRKAR1A gene, results from an A to T substitution at nucleotide position 51. The glutamic acid at codon 17 is replaced by aspartic acid, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001065796 | SCV001230780 | uncertain significance | Carney complex, type 1 | 2023-06-25 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 825535). 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. 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 has not been reported in the literature in individuals affected with PRKAR1A-related conditions. This variant is present in population databases (rs771518581, gnomAD 0.004%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 17 of the PRKAR1A protein (p.Glu17Asp). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001532888 | SCV001748669 | uncertain significance | not specified | 2021-06-21 | criteria provided, single submitter | clinical testing | Variant summary: PRKAR1A c.51A>T (p.Glu17Asp) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251456 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.51A>T in individuals affected with Carney Complex and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |