ClinVar Miner

Submissions for variant NM_000539.3(RHO):c.1033G>A (p.Val345Met)

dbSNP: rs104893795
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001045798 SCV001209671 pathogenic not provided 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 345 of the RHO protein (p.Val345Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (adRP) (PMID: 1808803, 1833777, 17488458, 28076437). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13056). 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 expected to disrupt RHO protein function with a positive predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on RHO function (PMID: 8253795, 9724753). This variant disrupts the p.Val345 amino acid residue in RHO. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24938718). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals RCV000013931 SCV001443258 likely pathogenic Retinitis pigmentosa 4 2020-09-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004814897 SCV005070205 pathogenic Retinal dystrophy 2022-01-01 criteria provided, single submitter clinical testing
OMIM RCV000013931 SCV000034178 pathogenic Retinitis pigmentosa 4 2001-08-01 no assertion criteria provided literature only

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