Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001875735 | SCV002156526 | uncertain significance | Hypertrophic cardiomyopathy | 2023-09-06 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1388062). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH7 protein function. 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. This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1679 of the MYH7 protein (p.Asn1679Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). |
| Ambry Genetics | RCV002334812 | SCV002641820 | uncertain significance | Cardiovascular phenotype | 2022-08-03 | criteria provided, single submitter | clinical testing | The p.N1679K variant (also known as c.5037C>G), located in coding exon 33 of the MYH7 gene, results from a C to G substitution at nucleotide position 5037. The asparagine at codon 1679 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in a population-based whole exome sequencing cohort; however, clinical histories were not provided (Yamaguchi-Kabata Y et al. J Hum Genet, 2018 Feb;63:213-230). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002478257 | SCV002791796 | uncertain significance | Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy | 2021-09-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003327530 | SCV004034892 | uncertain significance | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29192238) |