ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4589G>A (p.Arg1530Gln) (rs730880803)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158663 SCV000208598 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing p.Arg1530Gln (CGA>CAA): c.4589 G>A in exon 33 of the MYH7 gene (NM_000257.2). A variant of unknown significance has been identified in the MYH7 gene. The R1530Q variant has not been published as a mutation or as a benign polymorphism to our knowledge. The R1530Q 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 population. The R1530Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense mutations in nearby residues (H1524R, E1536K) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in HCM panel(s).
Invitae RCV000823461 SCV000964321 uncertain significance Hypertrophic cardiomyopathy 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1530 of the MYH7 protein (p.Arg1530Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs730880803, ExAC 0.001%). This variant has not been reported in the literature in individuals with MYH7-related disease. ClinVar contains an entry for this variant (Variation ID: 181259). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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