ClinVar Miner

Submissions for variant NM_000330.3(RS1):c.590G>A (p.Arg197His) (rs281865355)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411288 SCV000486798 likely pathogenic Juvenile retinoschisis 2016-08-10 criteria provided, single submitter clinical testing
GeneDx RCV000085338 SCV000589355 pathogenic not provided 2017-06-21 criteria provided, single submitter clinical testing The R197H missense variant in the RS1 gene has been reported previously in multiple unrelated individuals with X-linked retinoschisis (The Retinoschisis Consortium, 1998; Sadaka and Sisk, 2016; Sergeev et al., 2013). This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R197H variant is a conservative amino acid substitution, which should be unlikely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. In addition, missense variants in the same codon (R197S, R197C, R197P) and nearby residues (I194N, I195V, I199T, R200S, R200C, R200H) have been reported in the Human Gene Mutation Database in association with retinoschisis (Stenson et al., 2014; Inoue et al., 2000), supporting the functional importance of this region of the protein. We interpret R197H as a pathogenic variant.
Retina International RCV000085338 SCV000117475 not provided not provided no assertion provided not provided
SIB Swiss Institute of Bioinformatics RCV000411288 SCV000803478 likely pathogenic Juvenile retinoschisis 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Retinoschisis juvenile X-linked 1, in X-linked Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Observed in multiple unrelated patients. (PMID:17631851,29081674,27246168,28450823,19390641). PM5 => Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:17631851).

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