Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000545366 | SCV000623737 | likely pathogenic | Hypertrophic cardiomyopathy | 2022-11-29 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Glu1752 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25182012; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 181275). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1752 of the MYH7 protein (p.Glu1752Gly). |
| Ambry Genetics | RCV002336362 | SCV002643815 | uncertain significance | Cardiovascular phenotype | 2018-07-24 | criteria provided, single submitter | clinical testing | The p.E1752G variant (also known as c.5255A>G), located in coding exon 34 of the MYH7 gene, results from an A to G substitution at nucleotide position 5255. The glutamic acid at codon 1752 is replaced by glycine, an amino acid with similar properties. Alternate amino acid substitutions at this position, p.E1752K and p.E1752V, have been associated with hypertrophic cardiomyopathy (HCM) (Waldmüller S et al. Eur. J. Heart Fail., 2011 Nov;13:1185-92; Lee DD et al. Pediatr Cardiol, 2014 Dec;35:1474-7). 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. |