Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000536882 | SCV000623699 | uncertain significance | Hypertrophic cardiomyopathy | 2020-02-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 1175 of the MYH7 protein (p.Arg1175Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. In summary, this variant is a missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The frequency data for this variant (rs566368210) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a MYH7-related disease. |
| Agnes Ginges Centre for Molecular Cardiology, |
RCV000536882 | SCV001245118 | uncertain significance | Hypertrophic cardiomyopathy | 2018-02-23 | criteria provided, single submitter | research | MYH7 Arg1175Trp has been previously reported in a childhood myopathy case (Invitae, Pers. Comm.). We identified this variant in a HCM proband with a family history of HCM (segregation not possible). The variant is present at a low frequency in the Genome Aggregation Database (MAF= 0.00002, http://gnomad.broadinstitute.org/). In silico prediction tools SIFT, PolyPhen-HCM and MutationTaster predict this variant to be deleterious. In summary, based rarity in the general population and in silico tools predicting a deleterious affect we classify MYH7 Arg1175Trp as a variant of 'uncertain significance'. |