Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587428 | SCV000698034 | uncertain significance | not provided | 2017-03-27 | criteria provided, single submitter | clinical testing | Variant summary: The c.11A>G (p.Lys4Arg) in MAP2K1 gene is a missense change that involves a mildly conserved nucleotide and 4/5 in silico tools predict benign outcome. The variant of interest is located outside of any known functional domain and no functional studies implying the impact of this varian ton protein function have been published at the time of evaluation. The variant is absent from the control population dataset of ExAC (0/ 21980 chrs tested). Small numbers of sample in ExAC database indicate a low coverage site, therefore this data should be reviewed with caution. The variant is present in control population of gnomAD at a frequency of 0.00001208 (2/ 165522 chrs tested), which exceeds the maximal expected allele frequency for a pathogenic variant in this gene (0.0000025). The presence of the variant in presumably unaffected individual in gnomAD suggests a benign outcome, as mutations in MAP2K1 are extremely rare in hematologic malignancy (COSMIC). The variant has not, to our knowledge, been reported in affected individuals via published reports or by reputable databases/clinical laboratories. Taking together, the variant was classified as VUS until more evidence becomes available. |
| Labcorp Genetics |
RCV003539978 | SCV004285429 | uncertain significance | RASopathy | 2023-01-14 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt MAP2K1 protein function. ClinVar contains an entry for this variant (Variation ID: 496174). This variant has not been reported in the literature in individuals affected with MAP2K1-related conditions. This variant is present in population databases (rs761150136, gnomAD 0.004%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 4 of the MAP2K1 protein (p.Lys4Arg). |