Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035985 | SCV000059637 | uncertain significance | not specified | 2014-01-20 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
Invitae | RCV000456646 | SCV000546255 | pathogenic | Hypertrophic cardiomyopathy | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1921 of the MYH7 protein (p.Arg1921Gln). This variant is present in population databases (rs397516256, gnomAD 0.003%). This missense change has been observed in individuals with autosomal dominant dilated cardiomyopathy (PMID: 32746448; Invitae). ClinVar contains an entry for this variant (Variation ID: 43090). 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%. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000619475 | SCV000740056 | uncertain significance | Cardiovascular phenotype | 2022-03-03 | criteria provided, single submitter | clinical testing | The p.R1921Q variant (also known as c.5762G>A), located in coding exon 37 of the MYH7 gene, results from a G to A substitution at nucleotide position 5762. The arginine at codon 1921 is replaced by glutamine, an amino acid with highly similar properties. This variant has been detected in a dilated cardiomyopathy cohort; however, details were limited (Burstein DS et al. Pediatr Res. 2021 05;89(6):1470-1476). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV001804760 | SCV002053082 | uncertain significance | Cardiomyopathy | 2023-04-24 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 1921 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 32746448). This variant has been identified in 4/282754 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |