ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5030G>A (p.Arg1677His) (rs730880914)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158869 SCV000208804 uncertain significance not provided 2016-08-12 criteria provided, single submitter clinical testing The R1677H variant in the MYH7 gene was first identified via direct sequencing of the MYBPC3 and MYH7 genes in two individuals with DCM (Waldmuller et al., 2011). This variant was also identified in the heterozygous state in another individual with DCM who was evaluated with a multi-gene panel (Berge et al., 2014). However, for all reported individuals, additional clinical information, familial segregation information, and in vitro functional studies were not included. The R1677H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The R1677H 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. Therefore, it is unclear if R1677H is a pathogenic or benign variant.
Invitae RCV000799550 SCV000939218 uncertain significance Hypertrophic cardiomyopathy 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1677 of the MYH7 protein (p.Arg1677His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs730880914, ExAC 0.009%). This variant has been observed in several individuals affected with dilated cardiomyopathy (PMID: 21750094, 24111713). ClinVar contains an entry for this variant (Variation ID: 181393). 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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