Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158534 | SCV000208469 | uncertain significance | not provided | 2014-04-01 | criteria provided, single submitter | clinical testing | p.Glu806Lys (GAA>AAA): c.2416 G>A in exon 21 of the MYH7 gene (NM_000257.2). The E806K variant has not been published as a mutation or as a benign polymorphism to our knowledge. The E806K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E806K 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 across species. Missense mutations in nearby residues (A797T, A797P, L796F) have been reported in association with HCM, supporting the functional importance of this region of the protein. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in HCM panel(s). |
| Invitae | RCV001229876 | SCV001402336 | uncertain significance | Hypertrophic cardiomyopathy | 2019-10-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 806 of the MYH7 protein (p.Glu806Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. 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 is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 181184). This variant is not present in population databases (ExAC no frequency). |