Submissions for variant NM_033118.4(MYLK2):c.4G>A (p.Ala2Thr)

gnomAD frequency: 0.00143  dbSNP: rs117502839

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172569	SCV000055130	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039789	SCV000063478	uncertain significance	not specified	2017-07-10	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Ala2Thr varia nt in MYLK2 has been identified by our laboratory in 1 adult with DCM, 1 adult w ith HCM, 1 child with biventricular hypertrophy and dysfunction, and 1 child wit h possible LVNC/DCM who also carried a pathogenic variant in MYH7. The p.Ala2Thr variant has also been identified in 0.2% (143/72280) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSN P rs117502839). Arginine (Arg) at position 2 is not conserved in mice, which car ry a threonine (Thr) at this position, raising the possibility that this change may be tolerated. Additional computational prediction tools do not provide stron g support for or against an impact to the protein. In summary, while the clinic al significance of the p.Ala2Thr variant is uncertain, its frequency and lack of conservation in mice suggest that it is more likely to be benign.
GeneDx	RCV000172569	SCV000236030	likely benign	not provided	2021-05-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25188385, 26595808, 23861362, 26423924, 24503780)
Invitae	RCV001085211	SCV000544634	likely benign	Hypertrophic cardiomyopathy 1	2024-01-22	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852948	SCV000995694	likely benign	Cardiomyopathy; Long QT syndrome; Ventricular tachycardia	2019-05-08	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170848	SCV001333468	benign	Cardiomyopathy	2020-12-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039789	SCV002104031	likely benign	not specified	2022-02-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000172569	SCV004152562	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	MYLK2: BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001085211	SCV004562775	uncertain significance	Hypertrophic cardiomyopathy 1	2023-10-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003904951	SCV004733700	likely benign	MYLK2-related disorder	2019-07-11	criteria provided, single submitter	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).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000172569	SCV001926752	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000172569	SCV001951499	likely benign	not provided		no assertion criteria provided	clinical testing