Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000035994 | SCV000059646 | uncertain significance | not specified | 2015-08-21 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
| Invitae | RCV000471357 | SCV000546271 | uncertain significance | Hypertrophic cardiomyopathy | 2016-05-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 237 of the MYH7 protein (p.Arg237Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MYH7-related disease. ClinVar contains an entry for this variant (Variation ID: 43099). 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"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV000766650 | SCV000618119 | uncertain significance | not provided | 2017-08-01 | criteria provided, single submitter | clinical testing | The R237Q variant of uncertain significance in the MYH7 gene has been reported in one patient referred for hypertrophic cardiomyopathy (HCM) genetic testing (Walsh et al., 2017); however, additional clinical details and segregation information were not provided. Additionally, while a different nucleotide substitution at the same residue (R237W) has been reported in association with dilated cardiomyopathy, the proband also harbored a second possibly damaging variant (Hershberger et al., 2008), and thus, the pathogenicity of this variant has not been definitively determined. Nevertheless, the R237Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R237Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Finally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. |
| Ambry Genetics | RCV000617410 | SCV000736602 | uncertain significance | Cardiovascular phenotype | 2016-05-20 | criteria provided, single submitter | clinical testing | Insufficient evidence |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000766650 | SCV000924873 | uncertain significance | not provided | 2017-06-20 | no assertion criteria provided | provider interpretation |