ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4499G>C (p.Arg1500Pro) (rs121913647)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000192201 SCV000223106 pathogenic Myopathy, distal, 1 2015-03-12 no assertion criteria provided literature only
Invitae RCV000804244 SCV000944142 pathogenic Hypertrophic cardiomyopathy 2018-08-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 1500 of the MYH7 protein (p.Arg1500Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Laing early-onset distal myopathy (PMID: 15322983). ClinVar contains an entry for this variant (Variation ID: 14115). Experimental studies have shown that this missense change results in reduced thermodynamic stability and filament stability (PMID: 19854198). Additional experimental studies have shown that this variant leads to the formation of myosin aggregates (PMID: 22155079). Variants that disrupt the p.Arg1500 amino acid residue in MYH7 have been observed in affected individuals (PMID: 15556047, 18660445, 19412328, 24119082). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000192201 SCV000035429 pathogenic Myopathy, distal, 1 2004-10-01 no assertion criteria provided literature only

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