ClinVar Miner

Submissions for variant NM_003977.4(AIP):c.383G>A (p.Arg128His)

gnomAD frequency: 0.00002  dbSNP: rs267606550
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001021265 SCV001182857 likely benign Hereditary cancer-predisposing syndrome 2018-05-31 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001052633 SCV001216854 uncertain significance not provided 2023-11-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 128 of the AIP protein (p.Arg128His). This variant is present in population databases (rs267606550, gnomAD 0.009%). This missense change has been observed in individual(s) with acromegaly (PMID: 21753072). ClinVar contains an entry for this variant (Variation ID: 41176). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001052633 SCV005375568 uncertain significance not provided 2023-11-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in a patient with pituitary macroadenoma and acromegaly in published literature (PMID: 19556287); This variant is associated with the following publications: (PMID: 21753072, 29074612, 19556287)
GeneReviews RCV000034075 SCV000058005 not provided Somatotroph adenoma no assertion provided literature only

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