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

gnomAD frequency: 0.00004  dbSNP: rs121909124

Total submissions: 6

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 Laboratory Services, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000132648	SCV001199138	uncertain significance	not provided	2023-12-25	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 157 of the GUCA1B protein (p.Gly157Arg). This variant is present in population databases (rs121909124, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects GUCA1B function (PMID: 33812995). 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.
Dept Of Ophthalmology, Nagoya University	RCV003887857	SCV004707307	benign	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
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.