Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158040 | SCV000207975 | likely pathogenic | not provided | 2023-02-15 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously reported as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 33318037, 25370473, 22753777, 19156172, 26399658, 22177953, 29493581) |
Labcorp Genetics |
RCV003539802 | SCV004305416 | likely pathogenic | RASopathy | 2023-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 64 of the MAP2K2 protein (p.Val64Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Noonan syndrome (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 180912). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) did not meet the statistical confidence thresholds required to predict the impact of this variant on MAP2K2 function. 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. |