ClinVar Miner

Submissions for variant NM_000076.2(CDKN1C):c.670G>A (p.Ala224Thr) (rs528634940)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462429 SCV000541736 uncertain significance Beckwith-Wiedemann syndrome 2018-10-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 224 of the CDKN1C protein (p.Ala224Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs528634940, ExAC 0.6%). This variant has been reported in the literature as maternally inherited in an individual affected with Beckwith-Wiedemann syndrome (BWS); however, the clinical status of the mother was not available (PMID: 27977403). ClinVar contains an entry for this variant (Variation ID: 404246). 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 tolerated, 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.

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