ClinVar Miner

Submissions for variant NM_001122630.2(CDKN1C):c.611C>A (p.Ala204Asp)

gnomAD frequency: 0.00002  dbSNP: rs1060500176
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475530 SCV000541735 uncertain significance Beckwith-Wiedemann syndrome 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 215 of the CDKN1C protein (p.Ala215Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDKN1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 404245). 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 not expected to disrupt CDKN1C protein function with a negative predictive value of 80%. 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000475530 SCV002584783 uncertain significance Beckwith-Wiedemann syndrome 2022-08-02 criteria provided, single submitter clinical testing The CDKN1C c.644C>A (p.Ala215Asp) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with Beckwith-Wiedemann syndrome or IMAGE syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002481365 SCV002782590 uncertain significance Beckwith-Wiedemann syndrome; IMAGe syndrome 2022-05-17 criteria provided, single submitter clinical testing

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