ClinVar Miner

Submissions for variant NM_000539.3(RHO):c.759G>T (p.Met253Ile)

gnomAD frequency: 0.00004  dbSNP: rs756658659
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000729715 SCV000857401 uncertain significance not provided 2017-10-06 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000778676 SCV000915016 uncertain significance Retinitis pigmentosa 2017-08-23 criteria provided, single submitter clinical testing The RHO c.759G>T (p.Met253Ile) missense variant was reported in a homozygous state in one Turkish individual who was born of a consanguineous marriage and displayed typical retinitis pigmentosa (RP) with cystoid maculopathy (Collin et al. 2011). Both parents were heterozygous carriers of the variant and showed no symptoms of RP, indicating a recessive inheritance pattern. The p.Met253Ile variant was not found in 180 ethnically matched control alleles and is reported at a frequency of 0.000063 in the European (non-Finnish) population of the Genome Aggregation Database. The variant is located in a well-conserved residue in the sixth transmembrane domain of the protein. Based on the limited available evidence, the p.Arg77Gln variant is classified as a variant of unknown significance but suspicious for pathogenicity for nonsyndromic retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000729715 SCV001221519 uncertain significance not provided 2022-09-19 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on RHO function (PMID: 30977563). 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 RHO protein function. ClinVar contains an entry for this variant (Variation ID: 594435). This missense change has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 21217109). This variant is present in population databases (rs756658659, gnomAD 0.006%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 253 of the RHO protein (p.Met253Ile).
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001196773 SCV001367406 likely pathogenic Pigmentary retinal dystrophy 2018-10-15 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM1,PM2,PP2,PP3.
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals RCV001265204 SCV001443242 likely pathogenic Retinitis pigmentosa 4 2020-09-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000729715 SCV001552339 uncertain significance not provided no assertion criteria provided clinical testing

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