Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000215326 | SCV000272038 | uncertain significance | not specified | 2015-02-26 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Lys835Met variant in MYH7 has not been previously reported in individuals with cardiomyop athy or in large population studies. Lysine (Lys) at position 835 is highly cons erved in mammals and across evolutionarily distant species and the change to met hionine (Met) was predicted to be pathogenic using a computational tool clinical ly validated by our laboratory. This tool's pathogenic prediction is estimated t o be correct 94% of the time (Jordan 2011). In summary, while there is some susp icion for a pathogenic role, the clinical significance of the p.Lys835Met varian t is uncertain. |
Invitae | RCV001853465 | SCV002312652 | uncertain significance | Hypertrophic cardiomyopathy | 2021-03-26 | 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 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 not been reported in the literature in individuals with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 228903). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with methionine at codon 835 of the MYH7 protein (p.Lys835Met). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and methionine. |