ClinVar Miner

Submissions for variant NM_003977.4(AIP):c.827C>T (p.Ala276Val) (rs61741147)

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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 RCV000573085 SCV000672433 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-20 criteria provided, single submitter clinical testing The p.A276V variant (also known as c.827C>T), located in coding exon 6 of the AIP gene, results from a C to T substitution at nucleotide position 827. The alanine at codon 276 is replaced by valine, an amino acid with similar properties. Functional analysis demonstrates that this alteration results in rapid protein degradation compared to wild-type; rapid degradation was correlated with age of diagnosis of acromegaly in a subset of alterations identified in clinically affected individuals; however, p.A276V was not identified in an affected individual in this study (Hernandez-Ramirez LC et al. J. Clin. Endocrinol. Metab. 2016 08;101(8):3144-54). This amino acid position is well 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.
Fulgent Genetics,Fulgent Genetics RCV000765006 SCV000896189 uncertain significance Acroleukopathy, symmetric; Pituitary dependent hypercortisolism; Somatotroph adenoma 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001202575 SCV001373691 uncertain significance not provided 2020-10-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 276 of the AIP protein (p.Ala276Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs61741147, ExAC 0.01%). This variant has not been reported in the literature in individuals with AIP-related conditions. ClinVar contains an entry for this variant (Variation ID: 485056). This variant has been reported to affect AIP protein 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.

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