Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000596945 | SCV000705251 | uncertain significance | not provided | 2017-02-05 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000596945 | SCV001487410 | uncertain significance | not provided | 2024-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 8 of the RBP4 protein (p.Leu8Phe). This variant is present in population databases (rs11546956, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with RBP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 499650). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Department of Pathology and Laboratory Medicine, |
RCV000596945 | SCV001553675 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The RBP4 p.L8F variant was not identified in the literature but was identified in dbSNP (ID: rs11546956) and ClinVar (classified as uncertain significance by EGL Genetic Diagnostics). The variant was identified in control databases in 9 of 274106 chromosomes at a frequency of 0.00003283, and was observed at the highest frequency in the European (non-Finnish) population in 8 of 124154 chromosomes (freq: 0.00006444) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.L8 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; however this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. | |
| Institute of Human Genetics, |
RCV004817801 | SCV005071575 | uncertain significance | Retinal dystrophy | 2022-01-01 | no assertion criteria provided | clinical testing |