Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001071435 | SCV001236741 | uncertain significance | Hypertrophic cardiomyopathy | 2021-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1046 of the MYH7 protein (p.Met1046Arg). This variant is present in population databases (rs763760498, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 864287). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
Fulgent Genetics, |
RCV002482143 | SCV002786641 | uncertain significance | Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy | 2022-02-23 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004000201 | SCV004832134 | uncertain significance | Cardiomyopathy | 2023-06-08 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with arginine at codon 1046 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/282854 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |