Total submissions: 11
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001068637 | SCV001233760 | uncertain significance | Hypertrophic cardiomyopathy | 2023-05-03 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 862006). Disruption of this splice site has been observed in individual(s) with idiopathic ventricular fibrillation and myopathy (PMID: 29343803). This variant is present in population databases (rs112907315, gnomAD 0.003%). This sequence change affects a donor splice site in intron 4 of the MYH7 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH7 cause disease. |
| Color Diagnostics, |
RCV001179500 | SCV001344170 | uncertain significance | Cardiomyopathy | 2023-06-28 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +1 position of intron 4 of the MYH7 gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with idiopathic ventricular fibrillation and myopathy (PMID: 29343803). It has also been reported in an individual affected with ischemic cardiomyopathy and cardiac amyloidosis who also carried a pathogenic variant in the TTR gene (PMID: 36923113). This variant has been identified in 4/251260 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical relevance of loss-of-function MYH7 splice and truncation variants in autosomal dominant cardiovascular disorders is not clearly established. 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. |
| Gene |
RCV001576686 | SCV001803923 | uncertain significance | not provided | 2019-10-18 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29343803) |
| Ambry Genetics | RCV002451299 | SCV002617050 | uncertain significance | Cardiovascular phenotype | 2020-07-27 | criteria provided, single submitter | clinical testing | The c.345+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 2 of the MYH7 gene. This variant has been identified in an individual with idiopathic ventricular fibrillation and myopathy (Broendberg AK et al. Eur. J. Hum. Genet., 2018 03;26:303-313). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of MYH7 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003147583 | SCV003835495 | uncertain significance | Dilated cardiomyopathy 1S | 2022-09-09 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003147587 | SCV003835508 | uncertain significance | Hypertrophic cardiomyopathy 1 | 2022-09-09 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003320229 | SCV003835528 | uncertain significance | Myosin storage myopathy | 2022-09-09 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003147588 | SCV003835529 | uncertain significance | Myopathy, myosin storage, autosomal recessive | 2022-09-09 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003320229 | SCV003835530 | uncertain significance | Myosin storage myopathy | 2022-09-09 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003147586 | SCV003836484 | uncertain significance | MYH7-related skeletal myopathy | 2022-09-09 | criteria provided, single submitter | clinical testing | |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV001256695 | SCV001433096 | likely pathogenic | Conduction disorder of the heart | 2019-08-20 | flagged submission | clinical testing |