ClinVar Miner

Submissions for variant NM_002098.6(GUCA1B):c.469G>A (p.Gly157Arg) (rs121909124)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000007794 SCV000267352 uncertain significance Retinitis pigmentosa 48 2016-03-18 criteria provided, single submitter reference population
Illumina Clinical Services Laboratory,Illumina RCV000343566 SCV000463007 uncertain significance Retinitis pigmentosa 2017-07-18 criteria provided, single submitter clinical testing The GUCA1B c.469G>A (p.Gly157Arg) variant is a missense variant that has been reported in two publications. In a study that tested the GUCA1B gene in 63 Japanese patients with autosomal dominant retinitis pigmentosa (adRP), Sato et al. (2005) identified the p.Gly157Arg variant in three unrelated individuals. Family members of two of the individuals were also evaluated. In one family, the variant was also seen in three affected siblings and was absent in an unaffected sibling. In the second family, the variant was also detected in an unaffected parent. The authors suggest this condition may have incomplete penetrance and variable expressivity. Arai et al. (2015) evaluated 349 Japanese patients with inherited retinal dystrophies and identified the p.Gly157Arg variant in four unrelated individuals with adRP. The p.Gly157Arg variant was absent from 100 controls of Japanese descent (Sato et al. 2005), but it is reported at a relatively high frequency of 0.0015 in the East Asian population of the Exome Aggregation Consortium. Based on the evidence, the p.Gly157Arg variant is classified as a variant of unknown significance but suspicious for pathogeniciy for autosomal dominant retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000132648 SCV001199138 uncertain significance not provided 2020-10-08 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 157 of the GUCA1B protein (p.Gly157Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs121909124, ExAC 0.2%). This variant has been observed in individual(s) with clinical features of retinitis pigmentosa (PMID: 15452722). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7369). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
OMIM RCV000007794 SCV000027995 pathogenic Retinitis pigmentosa 48 2005-03-01 no assertion criteria provided literature only
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132648 SCV000172599 probable-non-pathogenic not provided no assertion criteria provided not provided Converted during submission to Likely benign.

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