ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2536G>C (p.Glu846Gln) (rs730880748)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172050 SCV000051006 uncertain significance Hypertrophic cardiomyopathy 2013-06-24 criteria provided, single submitter research
GeneDx RCV000158546 SCV000208481 pathogenic not provided 2013-02-13 criteria provided, single submitter clinical testing p.Glu846Gln (GAG>CAG): c.2536 G>C in exon 22 of the MYH7 gene (NM_000257.2). The Glu846Gln mutation in the MYH7 gene has been reported in association with HCM (Havndrup O et al., 2003; Ho C et al., 2009). Havndrup et al. identified Glu846Gln in one family with three affected individuals who harbored this mutation and it was not observed in 100 control individuals. Other asymptomatic carriers of this mutation were found in younger generations, which the authors suggested was due to reduced penetrance in this family. Mutations in this codon (Glu846Lys) and in nearby codons (Glu844Lys, Arg845Gly, Lys847Glu, Met849Thr) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, Glu846Gln 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. In summary, Glu846Gln in the MYH7 gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).
Ambry Genetics RCV000253031 SCV000319790 likely pathogenic Cardiovascular phenotype 2015-06-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Well-characterized mutation at same position,Moderate segregation with disease (at least 3 informative meioses) for rare diseases.

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