ClinVar Miner

Submissions for variant NM_001122630.2(CDKN1C):c.176C>T (p.Pro59Leu)

dbSNP: rs483352970
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269845 SCV001450146 likely pathogenic not provided 2015-12-10 criteria provided, single submitter clinical testing
GeneDx RCV001269845 SCV004169720 likely pathogenic not provided 2023-05-02 criteria provided, single submitter clinical testing Reported in a proband and affected mother, but the features of Beckwith-Wiedemann syndrome seen in these individuals were not delineated; the proband was also reported to have a de novo variant in another gene felt to be causative for the proband's profound intellectual disability (Hiraide et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10424811, 26077438, 33644862)
Labcorp Genetics (formerly Invitae), Labcorp RCV003502515 SCV004294090 pathogenic Beckwith-Wiedemann syndrome 2023-07-08 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 70 of the CDKN1C protein (p.Pro70Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Beckwith-Wiedemann syndrome (PMID: 10424811, 26077438). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as 1435C‚ÜíT and p.P59L.. ClinVar contains an entry for this variant (Variation ID: 132842). 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. For these reasons, this variant has been classified as Pathogenic.

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