Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000457580 | SCV000546258 | uncertain significance | Hypertrophic cardiomyopathy | 2023-07-07 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Lys615 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been observed in individuals with MYH7-related conditions (PMID: 1417858, 15563892), which suggests that this may be a clinically significant amino acid residue. This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 615 of the MYH7 protein (p.Lys615Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 407194). 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. 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. |