Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001324130 | SCV001515072 | uncertain significance | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 221 of the AIP protein (p.Pro221Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with AIP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1023999). 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%. 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. |
| St. |
RCV001775166 | SCV002012421 | uncertain significance | Familial isolated pituitary adenoma | 2021-10-12 | criteria provided, single submitter | clinical testing | The AIP c.662C>T (p.Pro221Leu) missense change has a maximum subpopulation frequency of 0.00089% in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/variant/11-67257803-C-T?dataset=gnomad_r2_1). Five of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with familial isolated pituitary adenoma. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting, BP4. |
| Ambry Genetics | RCV002366197 | SCV002664521 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-06 | criteria provided, single submitter | clinical testing | The p.P221L variant (also known as c.662C>T), located in coding exon 5 of the AIP gene, results from a C to T substitution at nucleotide position 662. The proline at codon 221 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well 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. |