ClinVar Miner

Submissions for variant NM_000539.3(RHO):c.647T>A (p.Met216Lys)

dbSNP: rs984572250
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001073436 SCV001238977 likely pathogenic Retinal dystrophy 2019-02-13 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001090666 SCV001246339 pathogenic not provided 2018-01-01 criteria provided, single submitter clinical testing
Invitae RCV001090666 SCV001377197 pathogenic not provided 2023-09-04 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 216 of the RHO protein (p.Met216Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 8081400; Invitae). ClinVar contains an entry for this variant (Variation ID: 865880). 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. Experimental studies have shown that this missense change affects RHO function (PMID: 30977563). This variant disrupts the p.Met216 amino acid residue in RHO. Other variant(s) that disrupt this residue have been observed in individuals with RHO-related conditions (PMID: 8081400, 22321012, 26962691), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals RCV001265200 SCV001443238 likely pathogenic Retinitis pigmentosa 4 2020-09-01 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001265200 SCV001573329 likely pathogenic Retinitis pigmentosa 4 2021-04-08 criteria provided, single submitter research The RHO c.647T>A variant was identified in an individual with retinitis pigmentosa with a presumed dominant inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PS3, PM1. Based on this evidence we have classified this variant as Likely Pathogenic.
Genomics England Pilot Project, Genomics England RCV001542566 SCV001760107 likely pathogenic Congenital stationary night blindness autosomal dominant 1 no assertion criteria provided clinical testing

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