Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001919641 | SCV002193998 | uncertain significance | 46,XY sex reversal 6 | 2021-03-08 | 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 MAP3K1 protein function. This variant has not been reported in the literature in individuals with MAP3K1-related conditions. While this variant is present in population databases (rs769918068), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with threonine at codon 55 of the MAP3K1 protein (p.Ala55Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. |