Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001027096 | SCV001189601 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | The p.Y268C variant (also known as c.803A>G), located in coding exon 6 of the AIP gene, results from an A to G substitution at nucleotide position 803. The tyrosine at codon 268 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in individuals with apparent sporadic pituitary macroadenomas (Tichomirowa MA et al. Eur. J. Endocrinol., 2011 Oct;165:509-15; Beckers A et al. Endocr. Rev., 2013 Apr;34:239-77). 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 not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001341744 | SCV001535633 | uncertain significance | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 268 of the AIP protein (p.Tyr268Cys). This variant is present in population databases (rs267606577, gnomAD 0.0009%). This missense change has been observed in individual(s) with a prolactinoma (PMID: 21753072). ClinVar contains an entry for this variant (Variation ID: 41206). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AIP protein function. 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. |
| Gene |
RCV000034105 | SCV000058035 | not provided | Somatotroph adenoma | no assertion provided | literature only |