Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000704590 | SCV000833543 | uncertain significance | RASopathy | 2023-04-07 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MAP2K2 protein function. ClinVar contains an entry for this variant (Variation ID: 40765). This variant has not been reported in the literature in individuals affected with MAP2K2-related conditions. 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 sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 9 of the MAP2K2 protein (p.Leu9Pro). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001251263 | SCV001426779 | uncertain significance | not specified | 2020-07-07 | criteria provided, single submitter | clinical testing | Variant summary: MAP2K2 c.26T>C (p.Leu9Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-06 in 155236 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.26T>C in individuals affected with Cardiofaciocutaneous Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002426539 | SCV002742840 | uncertain significance | Cardiovascular phenotype | 2021-10-21 | criteria provided, single submitter | clinical testing | The p.L9P variant (also known as c.26T>C), located in coding exon 1 of the MAP2K2 gene, results from a T to C substitution at nucleotide position 26. The leucine at codon 9 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Service de Génétique Moléculaire, |
RCV000824941 | SCV000965976 | uncertain significance | Noonan syndrome | no assertion criteria provided | clinical testing |