ClinVar Miner

Submissions for variant NM_003977.4(AIP):c.733G>A (p.Glu245Lys) (rs150645662)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001026294 SCV001188644 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-07 criteria provided, single submitter clinical testing The p.E245K variant (also known as c.733G>A), located in coding exon 5 of the AIP gene, results from a G to A substitution at nucleotide position 733. The glutamic acid at codon 245 is replaced by lysine, an amino acid with similar properties. This variant was identified in the germline of an individual with a prolactinoma that did not exhibit loss-of-heterozygosity for AIP (Cai F et al. Eur. J. Endocrinol., 2013 Dec;169:867-84). This amino acid position is poorly 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.
Illumina Clinical Services Laboratory,Illumina RCV001105892 SCV001262906 likely benign Somatotroph adenoma 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV001231533 SCV001404059 uncertain significance not provided 2020-09-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 245 of the AIP protein (p.Glu245Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs150645662, ExAC 0.06%). This variant has been observed in an individual affected with a prolactinoma (PMID: 24050928). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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