Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000647734 | SCV000769532 | likely pathogenic | Oligosynaptic infertility; 46,XY sex reversal 3 | 2018-01-18 | criteria provided, single submitter | clinical testing | This sequence change, c.1216_*339del, results in a partial exon deletion of the last exon in the NR5A1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 56 amino acids of the NR5A1 protein and results in a truncated protein product. This variant has not been reported in the literature in individuals with NR5A1-related disease. Other truncations (p.Tyr409*,p.Leu423Trpfs*7, and p.Glu445*) that lie downstream of this variant have been reported in individuals affected with 46, XY disorders of sexual development (PMID:28032338, 28326187). 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. |
| Invitae | RCV001378459 | SCV001576027 | likely pathogenic | Oligosynaptic infertility; 46,XY disorder of sex development | 2021-09-09 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 7 (c.1216_*339del) of the NR5A1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 82 amino acid(s) of the NR5A1 protein. This variant has not been reported in the literature in individuals affected with NR5A1-related conditions. This variant disrupts the C-terminus of the NR5A1 protein. Other variant(s) that disrupt this region (p.Tyr409*, p.Leu423Trpfs*7, p.Glu445*) have been observed in individuals with NR5A1-related conditions (PMID: 28032338, 28326187). This suggests that this may be a clinically significant region of the protein. 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. |