Submissions for variant NM_002900.3(RBP3):c.1141G>C (p.Glu381Gln)

gnomAD frequency: 0.00055  dbSNP: rs139299230

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000404738	SCV000362615	uncertain significance	Retinitis pigmentosa	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000519611	SCV000618704	uncertain significance	not provided	2017-07-06	criteria provided, single submitter	clinical testing	The E381Q variant in the RBP3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the E381Q variant is observed in 35/64528 (0.05%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The E381Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E381Q as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000519611	SCV001373759	uncertain significance	not provided	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 381 of the RBP3 protein (p.Glu381Gln). This variant is present in population databases (rs139299230, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with RBP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 299988). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Ambry Genetics	RCV002522158	SCV003685928	uncertain significance	Inborn genetic diseases	2021-09-16	criteria provided, single submitter	clinical testing	The c.1141G>C (p.E381Q) alteration is located in exon 1 (coding exon 1) of the RBP3 gene. This alteration results from a G to C substitution at nucleotide position 1141, causing the glutamic acid (E) at amino acid position 381 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000519611	SCV004700434	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing