ClinVar Miner

Submissions for variant NM_000554.6(CRX):c.268C>T (p.Arg90Trp)

gnomAD frequency: 0.00002  dbSNP: rs104894673
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001074643 SCV001240235 likely pathogenic Retinal dystrophy 2019-02-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001244346 SCV001417558 pathogenic Leber congenital amaurosis 7; Cone-rod dystrophy 2 2024-10-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 90 of the CRX protein (p.Arg90Trp). This variant is present in population databases (rs104894673, gnomAD 0.01%). This missense change has been observed in individuals with clinical features of CRX-related conditions (PMID: 9931337; internal data). ClinVar contains an entry for this variant (Variation ID: 7422). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CRX protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CRX function (PMID: 9931337, 11971869, 24516401). For these reasons, this variant has been classified as Pathogenic.
Pediatric/Medical Genetics, Ministry of Health, Qatif Central Hospital RCV000007847 SCV002765161 pathogenic Leber congenital amaurosis 7 2021-08-20 criteria provided, single submitter clinical testing
GeneDx RCV000086364 SCV003931077 likely pathogenic not provided 2022-12-01 criteria provided, single submitter clinical testing Observed in homozygous state in a patient with Leber congenital amaurosis in the literature (Swaroop et al., 1999) and not observed in homozygous state in controls; Published functional studies demonstrate a significant reduction in protein function with loss of DNA binding affinity and change in specificity (Swaroop et al., 1999; Barrera et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 24516401, 27013732, 11971869, 10887186, 9931337, 22113834, 31626798, 31054281, 32533067, 32689858)
OMIM RCV000007847 SCV000028052 pathogenic Leber congenital amaurosis 7 1999-02-01 no assertion criteria provided literature only
Retina International RCV000086364 SCV000118510 not provided not provided no assertion provided not provided
Laboratory of Genetics in Ophthalmology, Institut Imagine RCV000007847 SCV001425459 pathogenic Leber congenital amaurosis 7 no assertion criteria provided research
Dept Of Ophthalmology, Nagoya University RCV001074643 SCV004706298 uncertain significance Retinal dystrophy 2023-10-01 flagged submission research

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