ClinVar Miner

Submissions for variant NM_004064.4(CDKN1B):c.163G>A (p.Ala55Thr) (rs759665516)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468355 SCV000541774 uncertain significance Multiple endocrine neoplasia, type 4 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 55 of the CDKN1B protein (p.Ala55Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs759665516, ExAC 0.09%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with Zollinger-Ellison syndrome (gastrinoma), hepatic metastasis and primary hyperparathyroidism (PMID: 22026581). ClinVar contains an entry for this variant (Variation ID: 404276). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV001012527 SCV001172992 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-03 criteria provided, single submitter clinical testing Insufficient evidence

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