ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.2081G>A (p.Cys694Tyr) (rs137954284)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480360 SCV000565645 likely pathogenic not provided 2014-08-29 criteria provided, single submitter clinical testing The C694Y variant that is likely pathogenic was identified in the USH2A gene. The C694Y missense change in the USH2A gene has been reported as a novel variant in an individual with retinitis pigmentosa and it was absent from 360 controls (Clark et al., 2010). The C694Y variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in an external variant database. The C694Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, the loss of a Cysteine residue may affect disulfide bonds. This substitution occurs at a position that is well conserved across species. According to the Human Gene Mutation Database (HGMD) another missense mutation at a nearby codon (C691Y) has been reported in association with Usher syndrome (Stenson et al., 2009), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant; however, the possibility that it is a benign variant cannot be excluded.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000480360 SCV000701718 uncertain significance not provided 2016-10-14 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504759 SCV000598795 likely pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research

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