Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001366847 | SCV001563164 | uncertain significance | not provided | 2020-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with proline at codon 277 of the AIP protein (p.Ala277Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with a pituitary adenoma (PMID: 19556287). ClinVar contains an entry for this variant (Variation ID: 41212). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV004619193 | SCV005117534 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-27 | criteria provided, single submitter | clinical testing | The p.A277P variant (also known as c.829G>C), located in coding exon 6 of the AIP gene, results from a G to C substitution at nucleotide position 829. The alanine at codon 277 is replaced by proline, an amino acid with highly similar properties. This variant was reported in an individual with features consistent with AIP-related familial isolated pituitary adenoma (FIPA) (Jaffrain-Rea ML et al. Endocr Relat Cancer, 2009 Sep;16:1029-43). This alteration is located in the functional significant tetratricopeptide repeat domain of the AIP protein, and a structural analysis suggests it may disrupt packing of the hydrophobic core (Morgan RM et al. PLoS One, 2012 Dec;7:e53339). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000034111 | SCV000058041 | not provided | Somatotroph adenoma | no assertion provided | literature only |