Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001366846 | SCV001563163 | uncertain significance | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 241 of the AIP protein (p.Lys241Glu). This variant is present in population databases (rs267606573, gnomAD 0.008%). This missense change has been observed in individual(s) with familial isolated pituitary adenoma (PMID: 17244780). ClinVar contains an entry for this variant (Variation ID: 41200). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AIP protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on AIP function (PMID: 19366855, 20506337). 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 | RCV002371817 | SCV002668752 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-13 | criteria provided, single submitter | clinical testing | The p.K241E variant (also known as c.721A>G), located in coding exon 5 of the AIP gene, results from an A to G substitution at nucleotide position 721. The lysine at codon 241 is replaced by glutamic acid, an amino acid with similar properties. This alteration has been observed in patients with pituitary adenomas (Daly AF et al. J Clin Endocrinol Metab, 2007 May;92:1891-6; Jaffrain-Rea ML et al. Endocr Relat Cancer, 2009 Sep;16:1029-43). Protein functional studies have shown this alteration to be potentially deleterious to PDE4A5 interactions, but to not impair the AIP-RET interaction (Bolger GB et al. Endocr Relat Cancer, 2016 05;23:419-31; Igreja S et al. Hum Mutat, 2010 Aug;31:950-60; Vargiolu M et al. J Clin Endocrinol Metab, 2009 Jul;94:2571-8). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000034099 | SCV000058029 | not provided | Somatotroph adenoma | no assertion provided | literature only |