Submissions for variant NM_002397.5(MEF2C):c.109G>A (p.Val37Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003129165	SCV003805424	pathogenic	not provided	2023-02-22	criteria provided, single submitter	clinical testing	Identified in an individual with a neurodevelopmental disorder, but segregation and detailed clinical information were not provided (Wang et al., 2020); 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: 33004838)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003619820	SCV004375482	uncertain significance	Intellectual disability, autosomal dominant 20	2023-12-28	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 37 of the MEF2C protein (p.Val37Met). This variant is present in population databases (rs765658557, gnomAD 0.006%). This missense change has been observed in individual(s) with neurodevelopmental disorder (PMID: 33004838). ClinVar contains an entry for this variant (Variation ID: 2430632). 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 expected to disrupt MEF2C protein function with a positive predictive value of 95%. 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.