Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158613 | SCV000208548 | likely pathogenic | not provided | 2012-04-02 | criteria provided, single submitter | clinical testing | The Ser1199Arg variant in the MYH7 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. Ser1199Arg results in a semi-conservative amino acid substitution of a neutral, polar Serine with a positively charged Arginine at a residue that is conserved across species. In silico analysis predicts Ser1199Arg is probably damaging to the protein structure/function. Mutations in nearby codons (Arg1193Ser, Glu1205Lys) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. In addition, the NHLBI ESP Exome Variant Server reports Ser1199Arg was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, while the Ser1199Arg variant in the MYH7 gene is a good candidate for a disease-causing mutation, we cannot unequivocally determine the clinical significance of this variant with the clinical and molecular information available at this time. The variant is found in HCM panel(s). |