Submissions for variant NM_001122630.2(CDKN1C):c.40G>A (p.Val14Met)

dbSNP: rs758244300

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000794106	SCV000933495	uncertain significance	Beckwith-Wiedemann syndrome	2023-11-13	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 25 of the CDKN1C protein (p.Val25Met). This variant is present in population databases (rs758244300, gnomAD 0.002%). 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: 640965). 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.
Immunogenetics and Transplant Biology Service, University Hospital "Città della Salute e della Scienza di Torino"	RCV000794106	SCV004037600	uncertain significance	Beckwith-Wiedemann syndrome	2023-07-03	no assertion criteria provided	clinical testing