ClinVar Miner

Submissions for variant NM_001122630.2(CDKN1C):c.110C>T (p.Ala37Val)

dbSNP: rs774548414
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000474168 SCV000541746 uncertain significance Beckwith-Wiedemann syndrome 2023-10-19 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 48 of the CDKN1C protein (p.Ala48Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 404255). 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. 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 RCV000474168 SCV005689397 uncertain significance Beckwith-Wiedemann syndrome 2024-08-13 criteria provided, single submitter clinical testing The CDKN1C c.143C>T (p.Ala48Val) missense change has a maximum subpopulation frequency of 0.001% 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 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.

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