ClinVar Miner

Submissions for variant NM_005921.2(MAP3K1):c.556A>G (p.Arg186Gly)

dbSNP: rs1579750361
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp 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, University Hospital Muenster 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, Zhejiang University 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.

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