MYLK2 was first reported in relation to hypertrophic cardiomyopathy (HCM) in humans as early as 2001(Davis et al., 2001 PMID: 11733062). To date, at least 5 unique variants (4 missense, 1 synonymous) have been reported in 4 probands with hypertrophic cardiomyopathy (Davis et al., 2001, PMID: 11733062; Wang et al., 2018, PMID: 29978770; Gonzalez-Garay et al., 2013, PMID:24082139; Burstein et al., 2021, PMID:32746448). However, these probands also carry additional variants in genes implicated in hypertrophic cardiomyopathy, including MYH7 and MYBPC3. No segregation data is available. The mechanism for disease is unknown, but predicted to be gain of function (GOF) from functional assays performed by Davis et al., 2001. This gene-disease relationship is supported by expression studies showing restricted expression of MYLK2 in skeletal muscle and heart and biochemical functional studies. The original curation was performed by the Hypertrophic Cardiomyopathy Gene Curation Expert Panel (GCEP) and published on January 18, 2017. In summary, there is no scored genetic evidence, and no new convincing evidence has emerged that contradicts the gene-disease relationship. More evidence is needed to either support or entirely refute the role MYLK2 plays in this disease. This classification was re-evaluated and approved by the ClinGen Hereditary Cardiovascular Disease Gene Curation Expert Panel on February 8, 2023. As a result of this re-evaluation, the classification was changed from limited to disputed.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.