Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Clinical Services Laboratory, |
RCV001094116 | SCV000375042 | uncertain significance | Charcot-Marie-Tooth disease, type 4B2 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Gene |
RCV000713001 | SCV000565518 | uncertain significance | not provided | 2018-10-05 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SBF2 gene. The R1508C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1508C variant is observed in 7/6606 (0.1%) alleles from individuals of European Finnish background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server)]. The R1508C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000528673 | SCV000657964 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2019-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 1508 of the SBF2 protein (p.Arg1508Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs141108330, ExAC 0.1%) but has not been reported in the literature in individuals with an SBF2-related disease. ClinVar contains an entry for this variant (Variation ID: 306583). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Athena Diagnostics Inc | RCV000713001 | SCV000843564 | uncertain significance | not provided | 2018-04-06 | criteria provided, single submitter | clinical testing | |
| Molecular Genetics Laboratory, |
RCV001172803 | SCV001335872 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |