Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002656625 | SCV003540537 | uncertain significance | Inborn genetic diseases | 2022-12-06 | criteria provided, single submitter | clinical testing | The c.3275A>G (p.D1092G) alteration is located in exon 14 (coding exon 14) of the MAP3K1 gene. This alteration results from a A to G substitution at nucleotide position 3275, causing the aspartic acid (D) at amino acid position 1092 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003641055 | SCV004472196 | uncertain significance | 46,XY sex reversal 6 | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1092 of the MAP3K1 protein (p.Asp1092Gly). This variant is present in population databases (rs374418331, gnomAD 0.02%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MAP3K1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2219751). 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 MAP3K1 protein function. 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. |