ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.725C>G (p.Ser242Cys) (rs730880921)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158880 SCV000208815 likely pathogenic not provided 2014-09-30 criteria provided, single submitter clinical testing p.Ser242Cys (TCC>TGC): c.725 C>G in exon 8 of the MYH7 gene (NM_000257.2). A S242C variant that is likely pathogenic was identified in the MYH7 gene. It has not been published as a mutation or as a benign polymorphism to our knowledge. The S242C variant 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 addition, the S242C variant is a non-conservative amino acid substitution at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Moreover, missense mutations in nearby residues (V236I, D239N, R243C, R243H) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in DCM-CRDM panel(s).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000615531 SCV000712851 uncertain significance not specified 2017-01-20 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Ser242Cys variant in MYH7 has not been previously reported in individuals with cardiomyop athy or in large population studies, but has been reported in ClinVar (Variation ID:181400). Serine at position 242 is highly conserved in evolution and the cha nge to Cysteine was predicted to be pathogenic using a computational tool clinic ally validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, while there is some su spicion for a pathogenic role, the clinical significance of the p.Ser242Cys vari ant is uncertain.

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