ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2525G>A (p.Ser842Asn) (rs397516154)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035801 SCV000059452 uncertain significance not specified 2015-09-02 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Ser842Asn variant in MYH7 has not been previously reported in individuals with cardiomyop athy and was absent from large population studies. Serine (Ser) at position 842 is highly conserved in mammals and the change to asparagine (Asn) was predicted to be pathogenic using a computational tool clinically validated by our laborato ry. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Ser842Asn variant is uncertain.
GeneDx RCV000766435 SCV000208480 likely pathogenic not provided 2018-12-28 criteria provided, single submitter clinical testing The S842N likely pathogenic variant in the MYH7 gene has been reported in a patient referred for HCM genetic testing (Alfares et al., 2015). This variant has been identified in an unrelated individual referred for HCM genetic testing at GeneDx and segregated with cardiomyopathy in at least three members of this family. The S842N variant is not observed in large population cohorts (Lek et al., 2016). Additionally, this variant variant is located in the myosin motor domain, a region enriched with missense variants reported in association with cardiomyopathy (Kelly et al., 2018). However, the S842N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. In summary, S842N in the MYH7 gene is interpreted as a likely pathogenic variant.
Evolutionary and Medical Genetics Laboratory, Centre for Cellular and Molecular Biology RCV000148956 SCV000154205 unknown Familial cardiomyopathy no assertion criteria provided not provided Converted during submission to Uncertain significance.

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