Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000818584 | SCV000959204 | uncertain significance | 46,XY sex reversal 6 | 2022-07-05 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MAP3K1-related conditions. This variant is present in population databases (rs559360433, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1443 of the MAP3K1 protein (p.Ala1443Thr). ClinVar contains an entry for this variant (Variation ID: 661215). 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. This variant disrupts the p.Ala1443 amino acid residue in MAP3K1. Other variant(s) that disrupt this residue have been observed in individuals with MAP3K1-related conditions (PMID: 27899157), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. |