Submissions for variant NM_002449.5(MSX2):c.645G>A (p.Met215Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003026655	SCV003323595	uncertain significance	Cranium bifidum occultum	2023-08-10	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 215 of the MSX2 protein (p.Met215Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2106815). 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 MSX2 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.
Revvity Omics, Revvity	RCV003134589	SCV003808981	uncertain significance	not provided	2023-08-02	criteria provided, single submitter	clinical testing