ClinVar Miner

Submissions for variant NM_000539.3(RHO):c.745G>T (p.Glu249Ter)

gnomAD frequency: 0.00004  dbSNP: rs104893783
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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

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