ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5690G>A (p.Arg1897His) (rs727503240)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000151233 SCV000199101 uncertain significance not specified 2013-12-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Arg1897His variant in MYH7 has not been reported in individuals with cardiomyopathy or in l arge European American and African American populations (NHLBI exome sequencing project). Arginine (Arg) at position 1897 is highly conserved in evolution, and the change to histidine (His) is predicted to be pathogenic using a computationa l tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). This data supports th at the Arg1897His variant may be pathogenic but additional studies are needed to fully assess its clinical significance.
GeneDx RCV000158713 SCV000208648 likely pathogenic not provided 2013-11-01 criteria provided, single submitter clinical testing p.Arg1897His (CGC>CAC): c.5690 G>A in exon 39 of the MYH7 gene (NM_000257.2). The Arg1897His variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although Arg1897His results in a conservative amino acid substitution of one positively charged residue for another, the Arg1897 residue is conserved across species. In silico analysis predicts Arg1897His is probably damaging to the protein structure/function. Mutations in nearby residues (His1901Gln, Glu1902Lys) have been reported n association with DCM, further supporting the functional importance of this region of the protein. Furthermore, the Arg1897His 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. In summary, while Arg1897His is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in DCM-CRDM panel(s).
CeGaT Praxis fuer Humangenetik Tuebingen RCV000158713 SCV000493624 uncertain significance not provided 2016-07-31 criteria provided, single submitter clinical testing
Invitae RCV000477566 SCV000546189 uncertain significance Hypertrophic cardiomyopathy 2016-08-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1897 of the MYH7 protein (p.Arg1897His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. 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. ClinVar contains an entry for this variant (Variation ID: 164264). 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). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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