Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000620160 | SCV000736964 | uncertain significance | Cardiovascular phenotype | 2017-12-11 | criteria provided, single submitter | clinical testing | The p.N479D variant (also known as c.1435A>G), located in coding exon 13 of the MYH7 gene, results from an A to G substitution at nucleotide position 1435. The asparagine at codon 479 is replaced by aspartic acid, an amino acid with highly similar properties. Other alterations affecting the same amino acid, p.N479S (c.1436A>G) and p.N479T (c.1436A>C), have been reported in association with hypertrophic cardiomyopathy (HCM) (Richard P et al. Circulation, 2003 May;107:2227-32; Mook OR et al. J. Med. Genet., 2013 Sep;50:614-26). 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. |
| Invitae | RCV003586208 | SCV004248518 | uncertain significance | Hypertrophic cardiomyopathy | 2023-06-20 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Asn479 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12707239, 12820698, 27532257, 28356264). 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: 519050). 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 asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 479 of the MYH7 protein (p.Asn479Asp). |