ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1902C>T (p.Gly634=) (rs1566533700)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001068907 SCV001234042 uncertain significance Hypertrophic cardiomyopathy 2019-12-23 criteria provided, single submitter clinical testing This sequence change affects codon 634 of the MYH7 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MYH7 protein. 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. ClinVar contains an entry for this variant (Variation ID: 635224). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786170 SCV000924875 uncertain significance not provided 2017-03-31 no assertion criteria provided provider interpretation Given that there is no case data available for review, we consider this variant to be a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). This is a novel variant. There is no case data and it has not been reported in ClinVar. It is not present in population databases. According to the test report, "in silico splice prediction programs predict that this variant may alter splicing by creation of a weak cryptic donor site upstream of the natural splice donor site." However, loss of function variation in MYH7 is not a common mechanism of disease for cardiomyopathy. The glycine at codon 634 is conserved across species, as are neighboring amino acids. This codon is not present in Homburger et al 2016, so one cannot evaluate whether or not this codon is enriched for variation in HCM populations as compared to controls. There is no variation 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, Ashkenazi, Latino descent. Average coverage at this site is 86.9X and median coverage is 100X.

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