Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158741 | SCV000208676 | uncertain significance | not provided | 2017-01-09 | criteria provided, single submitter | clinical testing | The c.530+1 G>A variant has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. This variant destroys the canonical splice donor site in intron 6 and is predicted to cause abnormal gene splicing. The variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.530+1 G>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, although splice site mutations in the MYH7 gene have been reported in association with cardiomyopathy, the vast majority of mutations in MYH7 are missense changes. Furthermore, various studies have conflicting hypotheses regarding MYH7 haploinsufficiency leading to cardiomyopathy (Nishi H et al., 1995; Waldmuller S et al., 2011). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. |
| Invitae | RCV001038776 | SCV001202268 | uncertain significance | Hypertrophic cardiomyopathy | 2022-01-15 | 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: 181311). Disruption of this splice site has been observed in individual(s) with MYH7-related conditions (PMID: 31130284). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 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. |
| CHEO Genetics Diagnostic Laboratory, |
RCV001170748 | SCV001333353 | uncertain significance | Cardiomyopathy | 2018-03-02 | criteria provided, single submitter | clinical testing |