Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000621047 | SCV000736358 | uncertain significance | Cardiovascular phenotype | 2023-09-28 | criteria provided, single submitter | clinical testing | The p.D778N variant (also known as c.2332G>A), located in coding exon 19 of the MYH7 gene, results from a G to A substitution at nucleotide position 2332. The aspartic acid at codon 778 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been observed in individuals with MYH7-related-cardiomyopathy (Lu C et al. J Transl Med, 2018 Aug;16:241). 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769460 | SCV000900854 | likely pathogenic | Cardiomyopathy | 2015-09-15 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001172073 | SCV001335010 | likely pathogenic | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | MYH7: PM1, PM2, PM5, PP1:Moderate, PP3 |
Invitae | RCV001850224 | SCV002156497 | pathogenic | Hypertrophic cardiomyopathy | 2023-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 778 of the MYH7 protein (p.Asp778Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 30165862; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 181369). 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. This variant disrupts the p.Asp778 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12566107, 15358028, 21896538, 22112859; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Clinical Genetics Laboratory, |
RCV002251738 | SCV002522539 | likely pathogenic | Hypertrophic cardiomyopathy 1 | 2020-02-05 | criteria provided, single submitter | clinical testing | PM1, PM2, PM5, PP3 |