ClinVar Miner

Submissions for variant NM_003977.4(AIP):c.827C>T (p.Ala276Val)

gnomAD frequency: 0.00008  dbSNP: rs61741147
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573085 SCV000672433 likely benign Hereditary cancer-predisposing syndrome 2022-03-29 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.
Fulgent Genetics, Fulgent Genetics RCV000765006 SCV000896189 uncertain significance Acroleukopathy, symmetric; Pituitary dependent hypercortisolism; Somatotroph adenoma 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001202575 SCV001373691 uncertain significance not provided 2025-01-15 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 276 of the AIP protein (p.Ala276Val). This variant is present in population databases (rs61741147, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with AIP-related conditions. ClinVar contains an entry for this variant (Variation ID: 485056). 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 RCV001202575 SCV002571484 uncertain significance not provided 2024-03-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate a damaging effect: increased rate of protein degradation compared to wildtype (PMID: 27253664); This variant is associated with the following publications: (PMID: 21512261, 27253664)
Baylor Genetics RCV003465251 SCV004193517 uncertain significance Somatotroph adenoma 2024-03-29 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.