Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001052727 | SCV001216951 | uncertain significance | Hypertrophic cardiomyopathy | 2019-03-18 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 17 of the MYH7 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYH7-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH7 cause disease. 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. |
Color Diagnostics, |
RCV001185106 | SCV001351259 | uncertain significance | Cardiomyopathy | 2023-05-04 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +1 position of intron 17 of the MYH7 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has not been identified 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV001185106 | SCV004239444 | uncertain significance | Cardiomyopathy | 2023-03-03 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV001185106 | SCV004829471 | uncertain significance | Cardiomyopathy | 2023-05-16 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +1 position of intron 17 of the MYH7 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has not been identified 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. |