Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Petrovsky National Research Centre of Surgery, |
RCV000678262 | SCV000804201 | uncertain significance | Dilated cardiomyopathy 1S | 2018-08-28 | criteria provided, single submitter | research | We observed this de novo variant in a young female patient with neonatal manifestation of left ventricular noncompaction syndrome, heart failure, lowering of ejection fraction. Both her parents were healthy. We did not confirm paternity and maternity for this family, so variant p.E1439K does not meet ACMG criteria to be classified as likely pathogenic. Thus, our classification was based on absence from controls, multiple lines of computational evidence (PolyPhen2, SIFT, MutationTaster) and assumed de novo origin. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769449 | SCV000900842 | uncertain significance | Cardiomyopathy | 2017-06-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001371262 | SCV001567820 | uncertain significance | Hypertrophic cardiomyopathy | 2020-10-04 | criteria provided, single submitter | clinical testing | 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 560219). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 1349 of the MYH7 protein (p.Glu1349Lys). 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. |