ClinVar Miner

Submissions for variant NM_003977.4(AIP):c.562C>T (p.Arg188Trp)

gnomAD frequency: 0.00003  dbSNP: rs577617733
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001060020 SCV001224680 uncertain significance not provided 2024-12-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 188 of the AIP protein (p.Arg188Trp). This variant is present in population databases (rs577617733, gnomAD 0.02%). This missense change has been observed in individual(s) with pituitary adenoma (PMID: 27253664). ClinVar contains an entry for this variant (Variation ID: 854882). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt AIP protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects AIP function (PMID: 27253664). 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.
GeneDx RCV001060020 SCV002578494 uncertain significance not provided 2022-04-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate reduced protein half-life, but stability comparable to wildtype (Hernandez-Ramirez 2016); Observed in a child with pituitary macroadenoma (Hernandez-Ramirez 2016); This variant is associated with the following publications: (PMID: 27253664)
Ambry Genetics RCV002348437 SCV002649269 likely benign Hereditary cancer-predisposing syndrome 2022-12-08 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV005055152 SCV005688990 uncertain significance Somatotroph adenoma 2024-08-26 criteria provided, single submitter clinical testing The AIP c.562C>T (p.Arg188Trp) missense change has a maximum subpopulation frequency of 0.02% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function. This variant has been reported in an individual with a pituitary adenoma (PMID: 27253664). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.?

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