ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.3856C>T (p.Arg1286Trp)

gnomAD frequency: 0.00003  dbSNP: rs754054234
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001343015 SCV001536970 uncertain significance Retinitis pigmentosa 12; Leber congenital amaurosis 8 2022-09-06 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 1286 of the CRB1 protein (p.Arg1286Trp). This variant is present in population databases (rs754054234, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CRB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1039526). 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 CRB1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004609787 SCV005108981 uncertain significance Inborn genetic diseases 2024-05-24 criteria provided, single submitter clinical testing The c.3856C>T (p.R1286W) alteration is located in exon 10 (coding exon 10) of the CRB1 gene. This alteration results from a C to T substitution at nucleotide position 3856, causing the arginine (R) at amino acid position 1286 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001825890 SCV002090212 uncertain significance Leber congenital amaurosis 2020-12-22 no assertion criteria provided clinical testing

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