Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158867 | SCV000208802 | uncertain significance | not provided | 2017-11-29 | criteria provided, single submitter | clinical testing | The S1550F variant has not been published as pathogenic or been reported as benign to our knowledge. The S1550F variant is not observed in large population cohorts (Lek et al., 2016). It has been observed in one other individual with cardiomyopathy referred for cardiac genetic testing at GeneDx. The S1550F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Nevertheless, this variant has not been identified in a significant number of affected individuals, and there are no functional studies or segregation data available to clarify the role of this variant in disease. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
| Invitae | RCV001207738 | SCV001379103 | likely pathogenic | Hypertrophic cardiomyopathy | 2022-11-29 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ser1550 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. ClinVar contains an entry for this variant (Variation ID: 181391). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1550 of the MYH7 protein (p.Ser1550Phe). |