Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781514 | SCV000919603 | uncertain significance | not specified | 2018-01-04 | criteria provided, single submitter | clinical testing | Variant summary: The c.140G>A (p.Arg47Gln) in MAP2K1 gene is a missense variant involves a highly conserved nucleotide. The variant is located outside of any known functional domain or repeat and 3/5 in silico tools predict benign outcome, however no functional studies supporting these predictions were published at the time of evaluation. This variant is absent from the control dataset of gnomAD (~246118 chrs tested). The variant has been reported as a confirmed somatic event in several carcinoma tumors, but yet to be cited by reputable databases/clinical laboratories as a germline event. The variant was identified in a prenatal sample undergoing testing due to abnormal ultrasonic findings. However, the origin of the variant could not have been confirmed as parental studies were not performed. Taking together, the variant was classified as VUS, until new information becomes available. |
Labcorp Genetics |
RCV002535695 | SCV002933119 | uncertain significance | RASopathy | 2023-05-22 | 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: 633293). This missense change has been observed in individual(s) with clinical features of MAP2K1-related conditions (PMID: 29907801). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 47 of the MAP2K1 protein (p.Arg47Gln). |