Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000617464 | SCV000740224 | uncertain significance | Cardiovascular phenotype | 2017-09-18 | criteria provided, single submitter | clinical testing | The p.E45D variant (also known as c.135G>C), located in coding exon 1 of the MYH7 gene, results from a G to C substitution at nucleotide position 135. The glutamic acid at codon 45 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy cohort; however, clinical details were limited (Walsh R et al. Genet. Med. 2017;19:192-203). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV002531866 | SCV002961620 | uncertain significance | Hypertrophic cardiomyopathy | 2023-09-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 45 of the MYH7 protein (p.Glu45Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cariomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 520375). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |