Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000551446 | SCV000623677 | uncertain significance | Hypertrophic cardiomyopathy | 2021-02-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with lysine at codon 892 of the MYH7 protein (p.Gln892Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual with hypertrophic cardiomyopathy. However, in that individual a pathogenic allele was also identified in MYH7 which suggests that this c.2674C>A variant was not the primary cause of disease (PMID: 23283745). |