Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000035501 | SCV000059151 | uncertain significance | not specified | 2011-12-02 | criteria provided, single submitter | clinical testing | The Tyr842Cys variant has not been reported in the literature but has been detec ted in 1 individual with HCM who carried another pathogenic HCM variant. The Tyr 842Cys variant has not yet been detected in isolation in an affected individual and its effect can therefore not be determined without additional studies. This individual?s origin is reported to be Caucasian and the Tyr842CYs variant has n ot been identified in over 2000 Caucasian probands tested by our laboratory. Thi s low frequency is consistent with a pathogenic role. Tyrosine (Tyr) at position 842 is highly conserved in evolution, suggesting that a change would not be tol erated. This variant was also predicted to be pathogenic using a computational t ool, which was validated by our laboratory using a set of cardiomyopathy variant s with well-established clinical significance. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, the avail able evidence is consistent with a pathogenic role but insufficient to establish this with certainty. Additional data is needed to determine the clinical signif icance of this variant. |