Submissions for variant NM_001122630.2(CDKN1C):c.319C>G (p.Pro107Ala)

gnomAD frequency: 0.00023  dbSNP: rs772684721

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000628546	SCV000749448	uncertain significance	Beckwith-Wiedemann syndrome	2024-10-03	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 118 of the CDKN1C protein (p.Pro118Ala). This variant is present in population databases (rs772684721, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. 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: 524697). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
GeneDx	RCV001771845	SCV001993514	uncertain significance	not provided	2019-04-26	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV002483764	SCV002790321	likely benign	Beckwith-Wiedemann syndrome; IMAGe syndrome	2024-01-06	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000628546	SCV004212430	uncertain significance	Beckwith-Wiedemann syndrome	2023-10-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935740	SCV004747176	likely benign	CDKN1C-related disorder	2022-05-09	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).