Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000225729 | SCV000208677 | uncertain significance | not provided | 2023-10-23 | criteria provided, single submitter | clinical testing | Located in a region enriched with missense variants reported in association with HCM (PMID: 27532257, 29300372); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 21750094, 27532257, 29300372, 36243179, 35113650) |
Invitae | RCV000464574 | SCV000546193 | uncertain significance | Hypertrophic cardiomyopathy | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 178 of the MYH7 protein (p.Gly178Arg). This variant is present in population databases (rs730880156, gnomAD 0.004%). This missense change has been observed in individuals with clinical features of left ventricular noncompaction, dilated cardiomyopathy, and/or hypertrophic cardiomyopathy (PMID: 21750094, 27532257; Invitae). ClinVar contains an entry for this variant (Variation ID: 180432). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769466 | SCV000900861 | uncertain significance | Cardiomyopathy | 2022-01-07 | criteria provided, single submitter | clinical testing | |
Agnes Ginges Centre for Molecular Cardiology, |
RCV000157350 | SCV000996332 | uncertain significance | Left ventricular noncompaction cardiomyopathy | 2019-08-21 | criteria provided, single submitter | research | The MYH7 Gly178Arg has previously been identified in 1 HCM patient (Waldmuller S et al., 2011), 1 LVNC patient (Blueprint Genetics, ClinVar SCV000207087.1) and in at least 3 DCM patients (Genedx, ClinVar SCV000208677.6; Walsh R, et al., 2017). The variant frequency in the Genome Aggregation Database (http://gnomad.broadinstitute.org/) is low. We have identified the MYH7 Gly178Arg variant in a LVNC patient with a family history of disease (3 other affected members; genetic segregation not possible). Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to have a deleterious effect. Additionally PolyPhen-HCM, a tool specifically designed to predict the effects of missense variants in HCM genes (Jordan DM, et al., 2011), predicts this variant to cause disease. In summary, although MYH7 Gly178Arg is absent in the general population and in silico tools support a pathogenic role, further evidence is required to understand its role in LVNC and cardiomyopathy. Hence, we classify MYH7 Gly178Arg as a variant of "uncertain significance". |
Blueprint Genetics | RCV000157350 | SCV000207087 | uncertain significance | Left ventricular noncompaction cardiomyopathy | 2014-12-01 | no assertion criteria provided | clinical testing |