ClinVar Miner

Submissions for variant NM_004183.4(BEST1):c.652C>T (p.Arg218Cys) (rs281865238)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000086150 SCV000231676 likely pathogenic not provided 2014-06-17 criteria provided, single submitter clinical testing
GeneDx RCV000086150 SCV000490429 pathogenic not provided 2018-08-16 criteria provided, single submitter clinical testing The R218C missense variant in the BEST1 gene has been reported in association with Best's Macular Dystrophy (BMD) (Caldwell et al., 1999; Bakall et al., 1999). In vitro functional studies demonstrated that while the protein possessing the R218C variant still localized to the plasma membrane, it failed to increase the Ca2+ dependent anion permeability in transfected cells (Milenkovic et al., 2011). According to the Human Gene Mutation Database (HGMD), many other missense variants (L217F, R218S, R218G, R218H, Q220P) have been reported in this residue and in neighboring residues (Stenson et al., 2014). The R218C was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret R218C as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000763263 SCV000893901 pathogenic Bestrophinopathy, autosomal recessive; Vitelliform macular dystrophy type 2; Vitreoretinochoroidopathy; Retinitis pigmentosa 50 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000086150 SCV001205165 pathogenic not provided 2020-06-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 218 of the BEST1 protein (p.Arg218Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with either autosomal dominant Best vitelliform macular dystrophy (PMID: 28687848, 29781975) or autosomal recessive bestrophinopathy (PMID: 30593719). ClinVar contains an entry for this variant (Variation ID: 99735). This variant has been reported to affect BEST1 protein function (PMID: 21878505, 23825107). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073491 SCV001239034 pathogenic Retinal dystrophy 2019-03-31 criteria provided, single submitter clinical testing
Retina International RCV000086150 SCV000118294 not provided not provided no assertion provided not provided
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787543 SCV000926517 likely pathogenic Vitelliform macular dystrophy type 2 2018-04-01 no assertion criteria provided research

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