ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4835T>C (p.Leu1612Pro) (rs587779392)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000132752 SCV000223121 pathogenic Myopathy, distal, 1 2015-03-12 no assertion criteria provided literature only
Invitae RCV000459843 SCV000546201 uncertain significance Hypertrophic cardiomyopathy 2016-05-23 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1612 of the MYH7 protein (p.Leu1612Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Laing early onset distal myopathy (PMID: 24664454). ClinVar contains an entry for this variant (Variation ID: 143213). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change is located in a region of the MYH7 protein where a significant number of previously reported MYH7 missense mutations are found (PMID: 24664454). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. A family study may help clarify this finding.
Neurogenetics Laboratory,Royal Perth Hospital RCV000132752 SCV000119903 pathogenic Myopathy, distal, 1 2013-01-01 no assertion criteria provided clinical testing

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. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.