Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000547727 | SCV000623660 | likely pathogenic | Hypertrophic cardiomyopathy | 2023-05-25 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Gly716 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9062359, 12084606, 12707239, 12975413, 20031618, 20624503, 23283745, 24093860, 25935763). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 454350). This missense change has been observed in individual(s) with clinical features of MYH7-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 716 of the MYH7 protein (p.Gly716Glu). |
Laboratory for Molecular Medicine, |
RCV000610760 | SCV000712080 | uncertain significance | not specified | 2016-05-06 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly716Glu variant in MYH7 has not been previously reported in individuals with cardiomyop athy or in large population studies. However, another disease-causing variant at the same position (p.Gly716Arg) has been reported in individuals with HCM, sugg esting changes at this position are not tolerated. Additionally, this variant wa s predicted to be pathogenic using a computational tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, while there is some suspicion for a path ogenic role, the clinical significance of the p.Gly716Glu variant is uncertain. |