Submissions for variant NM_033118.4(MYLK2):c.425G>T (p.Gly142Val)

gnomAD frequency: 0.00006  dbSNP: rs56385445

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000805596	SCV000945556	uncertain significance	Hypertrophic cardiomyopathy 1	2022-11-15	criteria provided, single submitter	clinical testing	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. 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 MYLK2 protein function. ClinVar contains an entry for this variant (Variation ID: 650441). This variant has not been reported in the literature in individuals affected with MYLK2-related conditions. This variant is present in population databases (rs56385445, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 142 of the MYLK2 protein (p.Gly142Val).
Klaassen Lab, Charite University Medicine Berlin	RCV000853131	SCV000995843	uncertain significance	Left ventricular noncompaction cardiomyopathy	2019-07-03	criteria provided, single submitter	research
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798982	SCV002043647	benign	Cardiomyopathy	2020-10-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003489897	SCV004241266	likely benign	not specified	2023-12-03	criteria provided, single submitter	clinical testing