Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
St. |
RCV003154183 | SCV003843021 | uncertain significance | Noonan syndrome 9 | 2022-01-03 | criteria provided, single submitter | clinical testing | The SOS2 c.1209C>A (p.Cys403Ter) change is a nonsense variant that is predicted to cause premature protein truncation. The disease mechanism for SOS2 is gain-of-function caused by heterozygous missense changes, whereas protein-truncating and splice variants do not have an established correlation to disease (PMID: 26173643). This variant is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). To our knowledge, this variant has not been reported in individuals with Noonan syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |