ClinVar Miner

Submissions for variant NM_000257.3(MYH7):c.4522_4524delGAG (p.Glu1508del) (rs397516220)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217126 SCV000279295 pathogenic not provided 2015-12-31 criteria provided, single submitter clinical testing The c.4522_4524delGAG variant in the MYH7 gene has been reported previously in several multigenerationfamilies with Laing distal myopathy, including two affected individuals without a familyhistory of myopathy (Dubourg et al., 2011; Van den Bergh et al., 2014; Lamont et al., 2014; Naddaf etal., 2015; Reis et al., 2015). Some individuals also had co-morbid dilated cardiomyopathy (Dubourg etal., 2011; Lamont et al., 2014; Naddaf et al., 2015). The c.4522_4524delGAG variant causes anin-frame deletion of codon Glutamic acid 1508, denoted p.E1508del. The c.4522_4524delGAGvariant occurs within a coiled coil region of the protein that is conserved across species. Furthermore,this in-frame deletion was not observed in approximately 6500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. Therefore, we interpret c.4522_4524delGAG as a pathogenic variant
Invitae RCV000558675 SCV000623718 pathogenic Hypertrophic cardiomyopathy 2018-10-22 criteria provided, single submitter clinical testing This variant, c.4522_4524delGAG, results in the deletion of 1 amino acid of the MYH7 protein (p.Glu1508del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals and families affected with Laing distal myopathy, and distal myopathy associated with cardiomyopathy (PMID: 26094647, 21279644, 25695922, 24710723, 24664454). In one of these cases, this variant was shown to arise de novo (PMID: 21279644). ClinVar contains an entry for this variant (Variation ID: 43023). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000132748 SCV000059568 pathogenic Myopathy, distal, 1 2013-12-06 no assertion criteria provided clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Neurogenetics Laboratory,Royal Perth Hospital RCV000132748 SCV000120159 pathogenic Myopathy, distal, 1 2013-01-01 no assertion criteria provided clinical testing
GeneReviews RCV000132748 SCV000223115 pathogenic Myopathy, distal, 1 2015-03-12 no assertion criteria provided literature only

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