ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5560-7C>A (rs778224065)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542502 SCV000623745 uncertain significance Hypertrophic cardiomyopathy 2017-05-03 criteria provided, single submitter clinical testing This sequence change falls in intron 37 of the MYH7 gene. It does not directly change the encoded amino acid sequence of the MYH7 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MYH7-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786169 SCV000924867 uncertain significance not provided 2017-08-02 no assertion criteria provided provider interpretation This variant was seen in one patient in our center with acute onset heart failure. Testing was performed at Invitae. Given the lack of case data, rarity in population databases, and uncertain effect on protein product, we consider this variant a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). I could find no reports of this variant in association with disease in PubMed or Google. The lab report indicates it is a novel variant. Per the lab report: "Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies." Site is not well conserved in vertebrates, according to the UCSC browser. The variant is listed in 1 of 121,979 individuals listed in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. Specifically the variant has been seen in 1 of 55,783 European Non-Finnish individuals The average coverage at that site in gnomAD exomes is 86x and genomes is 33x.

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