Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756276 | SCV000884037 | uncertain significance | not provided | 2018-05-08 | criteria provided, single submitter | clinical testing | The p.Gly86Val variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Genome Aggregation Database (gnomAD). The glycine at position 86 is highly conserved up to tetraodon considering 12 species (Alamut v2.11) and computational analyses of the effects of the p.Gly86Val variant on protein structure and function provide conflicting results (SIFT: tolerated, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Gly86Val variant with certainty. |
| Invitae | RCV001350203 | SCV001544585 | uncertain significance | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E | 2020-11-16 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with INF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 618181). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 86 of the INF2 protein (p.Gly86Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |