ClinVar Miner

Submissions for variant NM_003977.4(AIP):c.769A>G (p.Ile257Val)

dbSNP: rs267606575
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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 RCV001237723 SCV001410496 uncertain significance not provided 2021-12-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 257 of the AIP protein (p.Ile257Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with AIP-related conditions (PMID: 20570174, 20685857). ClinVar contains an entry for this variant (Variation ID: 41204). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects AIP function (PMID: 20506337, 27253664, 30941100). 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.
Ambry Genetics RCV004018730 SCV005021259 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-13 criteria provided, single submitter clinical testing The p.I257V variant (also known as c.769A>G), located in coding exon 5 of the AIP gene, results from an A to G substitution at nucleotide position 769. The isoleucine at codon 257 is replaced by valine, an amino acid with highly similar properties. This alteration was identified in an individual with a pituitary macroadenoma (Daly AF et al. J Clin Endocrinol Metab, 2010 Nov;95:E373-83). A functional study suggests that the protein based on this alteration had a shorten half-life compared with the wild-type protein; however, the physiological relevance of this finding is unclear (Hernández-Ramírez LC et al. J Clin Endocrinol Metab, 2016 Aug;101:3144-54). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV001237723 SCV005325022 uncertain significance not provided 2023-09-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with pituitary adenomas (Daly et al., 2010; Chahal et al., 2010); This variant is associated with the following publications: (PMID: 30941100, 27267386, 31589614, 20570174, 20506337, 20457215, 27253664, 34588620, 20685857, 23300914, 23371967, 22720333)
GeneReviews RCV000034103 SCV000058033 not provided Somatotroph adenoma no assertion provided literature only

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