Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001007976 | SCV001167706 | likely pathogenic | not provided | 2019-02-26 | criteria provided, single submitter | clinical testing | The E249X variant in the RHO gene has been reported previously in association with autosomal recessive retinitis pigmentosa (Rosenfeld et al., 1992). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In vitro functional studies demonstrate reduction of mRNA levels, supporting degradation by nonsense-mediated mRNA decay (Hernan et al, 2011; Roman-Sanchez et al., 2016). The E249X variant is observed in 5/111696 (0.005%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). We interpret E249X as a likely pathogenic variant. |
Blueprint Genetics | RCV001074645 | SCV001240237 | likely pathogenic | Retinal dystrophy | 2019-02-20 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001007976 | SCV001587466 | pathogenic | not provided | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu249*) in the RHO gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RHO are known to be pathogenic (PMID: 1303237, 21174529). This variant is present in population databases (rs104893783, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 1303237). ClinVar contains an entry for this variant (Variation ID: 13036). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000013911 | SCV000034158 | pathogenic | Retinitis pigmentosa 4, autosomal recessive | 1992-06-01 | no assertion criteria provided | literature only |