ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1757T>C (p.Val586Ala) (rs397516121)

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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 RCV000035747 SCV000059398 likely pathogenic Hypertrophic cardiomyopathy 2018-05-25 criteria provided, single submitter clinical testing The p.Val586Ala variant in MYH7 has been identified in 2 individuals with HCM a nd segregated with disease in 3 affected relatives from one family (LMM data). I t has not been identified in large population studies. Computational prediction tools and conservation analysis suggest that the p.Val586Ala variant may impact the protein, though this information is not predictive enough to determine patho genicity. Of note, this variant lies in the head region of the protein. Missense variants in this region have been reported and statistically indicated to be mo re likely to cause disease (Walsh 2016). The above evidence supports a pathogeni c role; however, it should be noted that 6 reportedly unaffected family members (29 years and older) carried the variant, suggesting clinical variability or red uced penetrance. In summary, although additional studies are required to fully e stablish its clinical significance, the p.Val586Ala variant is likely pathogenic . ACMG/AMP Criteria applied: PM1, PM2, PP1, PP3, PS4_Supporting.

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