Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521554 | SCV000617292 | uncertain significance | not provided | 2017-08-21 | criteria provided, single submitter | clinical testing | The A1660E variant has been previously reported in an individual with dilated cardiomyopathy; however, additional detailed clinical information and segregation analysis was not provided (Waldmuller et al., 2011). The A1660E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Labcorp Genetics |
RCV000688117 | SCV000815717 | uncertain significance | Hypertrophic cardiomyopathy | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1660 of the MYH7 protein (p.Ala1660Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 21750094). ClinVar contains an entry for this variant (Variation ID: 449317). 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 not 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. |
| Fulgent Genetics, |
RCV002490901 | SCV002784085 | uncertain significance | Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy | 2021-08-31 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004003601 | SCV004836758 | uncertain significance | Cardiomyopathy | 2023-10-02 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with glutamic acid at codon 1660 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 21750094). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |