ClinVar Miner

Submissions for variant NM_004484.4(GPC3):c.1666G>A (p.Gly556Arg)

dbSNP: rs267606850
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002313704 SCV000849104 likely pathogenic Inborn genetic diseases 2017-05-26 criteria provided, single submitter clinical testing The p.G556R variant (also known as c.1666G>A), located in coding exon 8 of the GPC3 gene, results from a G to A substitution at nucleotide position 1666. The glycine at codon 556 is replaced by arginine, an amino acid with dissimilar properties. This alteration was detected in an individual diagnosed with Simpson-Golabi-Behmel syndrome (SGBS) who presented with ischemic stroke due to a dissection of the right internal cartoid artery (Pénisson-Besnier I et al. Am. J. Med. Genet. A, 2008 Feb;146A:464-7). In one functional study, authors showed that this alteration may reduce the ability of GPC3 protein to inhibit Hedgehog signaling during development (Shi W et al. Am. J. Med. Genet. A, 2009 Mar;149A:552-4). In addition, this alteration was detected in two unrelated individuals from a cohort of patients with SGBS phenotypes; however, specific clinical information on these two individuals was not provided (Cottereau E et al. Am J Med Genet C Semin Med Genet, 2013 May;163C:92-105). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
GeneDx RCV005055511 SCV005689870 pathogenic not provided 2024-08-08 criteria provided, single submitter clinical testing Published functional studies demonstrate that this variant impairs the function of the GPC3 protein (PMID: 19215053); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31826854, 18203194, 29637653, 34547244, 23606591, 19215053)
OMIM RCV000012461 SCV000032695 pathogenic Simpson-Golabi-Behmel syndrome type 1 2009-03-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.