ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.635G>A (p.Cys212Tyr)

dbSNP: rs1658699227
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001240151 SCV001413075 uncertain significance Retinitis pigmentosa 12; Leber congenital amaurosis 8 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 212 of the CRB1 protein (p.Cys212Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Stargardt macular dystrophy (PMID: 25474345). ClinVar contains an entry for this variant (Variation ID: 965648). 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 expected to disrupt CRB1 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002491791 SCV002789834 uncertain significance Pigmented paravenous retinochoroidal atrophy; Retinitis pigmentosa 12; Leber congenital amaurosis 8 2022-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449747 SCV004178841 uncertain significance Leber congenital amaurosis 8 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449748 SCV004178842 uncertain significance Pigmented paravenous retinochoroidal atrophy 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449746 SCV004178843 uncertain significance Retinitis pigmentosa 12 2023-04-11 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004545145 SCV004758873 likely pathogenic CRB1-related disorder 2024-06-27 no assertion criteria provided clinical testing The CRB1 c.635G>A variant is predicted to result in the amino acid substitution p.Cys212Tyr. This variant has been reported in the compound heterozygous state in an individual with retinal dystrophy (Zaneveld et al. 2015. PubMed ID: 25474345). This variant has been detected here, at PreventionGenetics, along with a second CRB1 variant in multiple individuals undergoing testing for retinal dystrophy (internal data). An alternate substitution of this amino acid (p.Cys212Phe) has also been reported along with a second CRB1 variant in an individual with retinal dystrophy (Del Pozo-Valero et al. 2022. PubMed ID: 35119454). This variant has not been reported in the large population database gnomAD, indicating this variant is rare. Given the evidence, we interpret this variant as likely pathogenic.

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