ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3407G>A (p.Arg1136His) (rs730880905)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766446 SCV000208794 uncertain significance not provided 2015-03-18 criteria provided, single submitter clinical testing This variant is denoted p.Arg1136His (R1136H) at the protein level and c.3407 G>A at the cDNA level. The Arg1136His variant has also not been reported as a disease-causing mutation or as a benign polymorphism, to our knowledge. Arg1136His results in a conservative substitution of one positively charged amino acid with another, however occurs at the Arginine1136 residue which is highly conserved across species. The nearest reported pathogenic mutations associated with cardiomyopathy are Leu1135Arg and Arg1193Ser. In silico analysis predicts Arg1136His to be damaging to the protein structure/function. Furthermore, Arg1136His was not identified in 502 control alleles from individuals of various ethnic backgrounds tested at GeneDx, indicating that it is not a common benign variant. In summary, with the clinical and molecular information available at this time, we cannot determine with certainty if Arg1136His is a disease-causing mutation or rare benign variant. The variant is found in HCM panel(s).
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000623814 SCV000740373 uncertain significance Primary familial hypertrophic cardiomyopathy 2016-07-28 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000158859 SCV000280339 uncertain significance not specified 2013-01-07 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Arg1136His in MYH7 This variant is novel. This is a conservative amino acid substitution with a polar Arginine replaced with a polar Histidine. Arginine is highly conserved at this position and in-silico analysis predicts the substitution to be damaging to the beta myosin heavy chain protein. One neighboring variant (p.Leu1135Arg) has been reported in association with cardiomyopathy. GeneDx reports that the variant was absent in 251 presumably healthy controls with mixed ancestry. It is not listed in dbSNP, 1000 Genomes or NHLBI’s Human Exome Variant Database, which includes MYH7 variant data on ~5,350 individuals of Caucasian and African American ancestry (as of December 2011).

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