Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569018 | SCV000672441 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | The p.R106C variant (also known as c.316C>T), located in coding exon 3 of the AIP gene, results from a C to T substitution at nucleotide position 316. The arginine at codon 106 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a 31-year-old male with a pituitary adenoma and family history of hyperparathyroidism and was classified as a variant of uncertain significance; this individual was also found to carry a missense alteration in the MEN1 gene that was classified as likely benign by the authors of the study (De Sousa SM et al. Eur. J. Endocrinol., 2017 May;176:635-644). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001236396 | SCV001409119 | uncertain significance | not provided | 2022-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 106 of the AIP protein (p.Arg106Cys). This variant is present in population databases (rs369414668, gnomAD 0.007%). This missense change has been observed in individual(s) with pituitary adenoma (PMID: 28220018). ClinVar contains an entry for this variant (Variation ID: 485059). 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. |
| Baylor Genetics | RCV003465252 | SCV004195871 | uncertain significance | Somatotroph adenoma | 2023-07-29 | criteria provided, single submitter | clinical testing |