ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1633G>A (p.Asp545Asn) (rs564101364)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000243487 SCV000320638 likely pathogenic Cardiovascular phenotype 2015-12-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Good segregation with disease (lod 1.5-3 = 5-9 meioses),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000553630 SCV000623649 uncertain significance Hypertrophic cardiomyopathy 2018-09-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 545 of the MYH7 protein (p.Asp545Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with left ventricular non-compaction cardiomyopathy (LVNC) in a family (PMID: 17947214) and was reported in at least one individual with dilated cardiomyopathy (PMID: 23349452). However, in both reports this variant was shown to occur in combination with another MYH7 variant, p.Asp955Asn, and in the familial study these variants were confirmed to be on the same chromosome (in cis). Additionally, both variants were also reported in a study of individuals affected with LVNC. It is not clear if the variants were observed in the same individual (PMID: 20965760). ClinVar contains an entry for this variant (Variation ID: 264607). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C15"). This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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.

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.