ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5606A>G (p.Asp1869Gly) (rs730880824)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000168920 SCV000208647 uncertain significance not provided 2018-06-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH7 gene. The D1869G variant has been published in at least one patient with HCM (Homburger et al., 2016); however, additional clinical details and segregation information were not provided. Nevertheless, this variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D1869G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Illumina Clinical Services Laboratory,Illumina RCV000290558 SCV000385876 uncertain significance Left ventricular noncompaction cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000329194 SCV000385877 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000376895 SCV000385878 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000284161 SCV000385879 uncertain significance Scapuloperoneal myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000341468 SCV000385880 uncertain significance Myosin storage myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000379698 SCV000385881 uncertain significance Myopathy, distal, 1 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000376895 SCV000546231 uncertain significance Hypertrophic cardiomyopathy 2016-08-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 1869 of the MYH7 protein (p.Asp1869Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs730880824, ExAC <0.01%) but has not been reported in the literature in individuals with a MYH7-related disease. ClinVar contains an entry for this variant (Variation ID: 181288). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function and mRNA splicing. It has been classified as a Variant of Uncertain Significance.

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