ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.507A>T (p.Arg169Ser) (rs397516238)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000035949 SCV000059600 likely pathogenic Hypertrophic cardiomyopathy 2017-12-15 criteria provided, single submitter clinical testing p.Arg169Ser, c.507A>T (MYH7; NM_000257.2; Chr14g.23901711T>A; GRCh37): The p.Arg 169Ser variant in MYH7 has not been previously reported in individuals with HCM and was absent from large population studies. Arginine (Arg) at position 169 is highly conserved in mammals and across evolutionarily distant species and the ch ange to Serine (Ser) was predicted to be pathogenic using a computational tool c linically validated by our laboratory. This tool's pathogenic prediction is esti mated to be correct 94% of the time (Jordan 2011). Of note, this variant lies in the head region of the protein. Missense variants in this region have been repo rted and statistically indicated to be more likely to cause disease (Walsh 2016) . In addition, two other amino acid substitutions involving this codon, p.Arg169 Gly and p.Arg169Lys, have also been identified in affected individuals (Maron 20 09, LMM data). In summary, although additional studies are required to fully est ablish its clinical significance, the p.Arg169Ser variant is likely pathogenic. ACMG/AMP Criteria applied: PM1, PM2, PM5, PP3.

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