Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000804251 | SCV000944151 | likely pathogenic | 46,XY sex reversal 6 | 2018-08-24 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed to be de novo in an individual affected with 46,XY disorder of sexual development (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 186 of the MAP3K1 protein (p.Arg186Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. |
Institute of Human Genetics, |
RCV003128418 | SCV003804839 | likely pathogenic | See cases | 2021-12-20 | criteria provided, single submitter | clinical testing | ACMG categories: PS1,PM2,PP3,PP5 |
Cell and Gene Engineering Laboratory, |
RCV000804251 | SCV001737544 | pathogenic | 46,XY sex reversal 6 | 2019-11-07 | no assertion criteria provided | clinical testing | The Arg186Gly variant in MAP3K1 has been reported in a girl with 46,XY complete gonadal dysgenesis in our studies which is being submitting. Additionally, in vitro functional studies indicated that the Arg186Gly variant activates ovarian-specific pathways and inhibits testicular-specific pathways. In summary, this results indicates classification of this variant as pathogenic. |