ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5027G>A (p.Arg1676Gln) (rs1451176863)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658395 SCV000780167 uncertain significance not provided 2018-05-24 criteria provided, single submitter clinical testing The R1676Q variant of uncertain significance in the MYH7 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). R1676Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Invitae RCV000542901 SCV000623731 uncertain significance Hypertrophic cardiomyopathy 2017-04-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1676 of the MYH7 protein (p.Arg1676Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA 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 novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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