Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV002251245 | SCV002521808 | uncertain significance | 46,XY sex reversal 3 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.61; 3Cnet: 0.08). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with NR5A1 related disorder (PMID: 29095814). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. |
| Invitae | RCV003774735 | SCV004577098 | uncertain significance | Oligosynaptic infertility; 46,XY disorder of sex development | 2023-06-05 | 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 NR5A1 protein function. ClinVar contains an entry for this variant (Variation ID: 1687563). This missense change has been observed in individual(s) with 46XY sex reversal (PMID: 29095814, 33351340). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 241 of the NR5A1 protein (p.Arg241Trp). |