Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000222375 | SCV000272043 | uncertain significance | not specified | 2015-04-13 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Met1046Il e variant in MYH7 has not been previously reported in individuals with cardiomyo pathy, but has been identified in 3/66740 European chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201195256). Me thionine (Met) at position 1046 is highly conserved in mammals and is moderately conserved across evolutionarily distant species and the change to isoleucine (I le) was predicted to be pathogenic using a computational tool clinically validat ed by our laboratory. This tool's pathogenic prediction is estimated to be corre ct 94% of the time (Jordan 2011). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Met1046Ile variant is unce rtain. |
| Color Diagnostics, |
RCV000776202 | SCV000911339 | uncertain significance | Cardiomyopathy | 2018-10-04 | criteria provided, single submitter | clinical testing | Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the neck and hinge region (S2 domain) of the MYH7 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been reported in an individual affected with hypertrophic cardiomyopathy in a public database (www.cardiodb.org). This variant has also been identified in 3/246258 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively. |
| Invitae | RCV001057776 | SCV001222288 | uncertain significance | Hypertrophic cardiomyopathy | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1046 of the MYH7 protein (p.Met1046Ile). This variant is present in population databases (rs201195256, gnomAD 0.0009%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 228907). 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 expected to disrupt MYH7 protein function with a positive predictive value of 95%. 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. |
| Baylor Genetics | RCV001329731 | SCV001521251 | uncertain significance | Dilated cardiomyopathy 1S | 2020-05-05 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |