Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158047 | SCV000207982 | likely pathogenic | not provided | 2014-02-03 | criteria provided, single submitter | clinical testing | p.Gly263Arg (GGA>AGA): c.787 G>A in exon 7 of the MAP2K2 gene (NM_030662.3). The G263R missense change has not been previously reported as a disease-causing mutation or as a benign polymorphism, to our knowledge. The G263R missense change is a non-conservative amino acid substitution with a non-polar and neutral residue (Gly) being replaced by a polar and positively charged residue (Arg). The residue at which this substitution occurs is highly conserved. Another missense mutation (K273R) has been reported at a nearby residue. The G263R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the majority of missense changes in MAP2K2 are pathogenic mutations, the potential for benign coding variants to exist in this gene must be considered. This variant has been observed to be paternally inherited. The variant is found in NOONAN panel(s). |
Ce |
RCV000158047 | SCV001501214 | uncertain significance | not provided | 2020-12-01 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV002247552 | SCV002518212 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005055639 | SCV005717037 | uncertain significance | RASopathy | 2024-11-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 263 of the MAP2K2 protein (p.Gly263Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MAP2K2-related conditions. ClinVar contains an entry for this variant (Variation ID: 180914). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt MAP2K2 function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |