ClinVar Miner

Submissions for variant NM_003977.4(AIP):c.782A>G (p.Tyr261Cys)

gnomAD frequency: 0.00001  dbSNP: rs780149133
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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 RCV001026851 SCV001189316 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-11 criteria provided, single submitter clinical testing The p.Y261C variant (also known as c.782A>G), located in coding exon 5 of the AIP gene, results from an A to G substitution at nucleotide position 782. The tyrosine at codon 261 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001039474 SCV001203006 uncertain significance not provided 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 261 of the AIP protein (p.Tyr261Cys). This variant is present in population databases (rs780149133, gnomAD 0.003%). 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: 827274). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AIP protein function with a positive predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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.
Baylor Genetics RCV004570076 SCV005059590 uncertain significance Somatotroph adenoma 2023-12-28 criteria provided, single submitter clinical testing

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