ClinVar Miner

Submissions for variant NM_019098.5(CNGB3):c.1672G>T (p.Gly558Cys)

gnomAD frequency: 0.00007  dbSNP: rs749413012
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001058379 SCV001222945 uncertain significance not provided 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 558 of the CNGB3 protein (p.Gly558Cys). This variant is present in population databases (rs749413012, gnomAD 0.04%). This missense change has been observed in individual(s) with achromatopsia or retinitis pigmentosa (PMID: 15712225). ClinVar contains an entry for this variant (Variation ID: 554831). 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 CNGB3 protein function. Experimental studies have shown that this missense change affects CNGB3 function (PMID: 26106334). 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.
Myriad Genetics, Inc. RCV000670529 SCV002060217 uncertain significance Achromatopsia 3 2021-11-10 criteria provided, single submitter clinical testing NM_019098.4(CNGB3):c.1672G>T(G558C) is a missense variant classified as a variant of uncertain significance in the context of CNGB3-related achromatopsia. G558C has been observed in cases with relevant disease (PMID: 15712225, 28224992, 28005958). Functional assessments of this variant are available in the literature (PMID: 26106334). G558C has been observed in population frequency databases (gnomAD: AMR 0.04%). In summary, there is insufficient evidence to classify NM_019098.4(CNGB3):c.1672G>T(G558C) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000678547 SCV000804625 uncertain significance Retinitis pigmentosa 2016-09-01 no assertion criteria provided clinical testing
Natera, Inc. RCV001272481 SCV001454543 uncertain significance Achromatopsia 2020-09-16 no assertion criteria provided clinical testing

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