Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000034065 | SCV000373575 | uncertain significance | Somatotroph adenoma | 2017-04-27 | criteria provided, single submitter | clinical testing | The API c.174G>C (p.Lys58Asn) missense variant has been reported in at least two studies in which it is found in two patients with pituitary macroadenoma in a heterozygous state (Tichomirowa et al. 2011; Cazabat L. 2012). The p.Lys58Asn variant was absent from 360 controls but is reported at a frequency of 0.00003 in the European (non-Finnish) population of the Exome Aggregation Consortium, though this is based on only two alleles but in a region of good sequence coverage. Based on the limited evidence, p.Lys58Asn variant is classified as a variant of uncertain significance but suspicious for pathogenicity for familial isolated pituitary adenomas. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Ambry Genetics | RCV001012978 | SCV001173508 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-28 | criteria provided, single submitter | clinical testing | The p.K58N variant (also known as c.174G>C), located in coding exon 2 of the AIP gene, results from a G to C substitution at nucleotide position 174. The lysine at codon 58 is replaced by asparagine, an amino acid with similar properties. This alteration has been reported in multiple individuals with pituitary macroadenoma (Tichomirowa MA et al. Eur. J. Endocrinol., 2011 Oct;165:509-15; Cazabat L et al. J. Clin. Endocrinol. Metab., 2012 Apr;97:E663-70; Cuny T et al. Eur. J. Endocrinol., 2013 Apr;168:533-41). This amino acid position is highly 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. |
Invitae | RCV001038333 | SCV001201799 | uncertain significance | not provided | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 58 of the AIP protein (p.Lys58Asn). This variant is present in population databases (rs267606539, gnomAD 0.002%). This missense change has been observed in individual(s) with pituitary adenoma (PMID: 21753072, 22319033, 23321498). ClinVar contains an entry for this variant (Variation ID: 41166). 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. |
Gene |
RCV001038333 | SCV003933386 | uncertain significance | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with isolated sporadic pituitary adenomas (Tichomirowa et al., 2011; Cazabat et al., 2012); This variant is associated with the following publications: (PMID: 21753072, 23371967, 22319033, 23321498, 31351448) |
Baylor Genetics | RCV000034065 | SCV004195316 | uncertain significance | Somatotroph adenoma | 2023-10-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000034065 | SCV000057995 | not provided | Somatotroph adenoma | no assertion provided | literature only |