Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001002004 | SCV001159820 | uncertain significance | Charcot-Marie-Tooth disease type 4B3 | 2018-08-05 | criteria provided, single submitter | clinical testing | The SBF1 c.4639C>T; p.Arg1547Trp variant (rs370182117), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the general population with an overall allele frequency of 0.03% (75/276800 alleles) in the Genome Aggregation Database. The arginine at codon 1547 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Arg1547Trp variant is uncertain at this time. |
Gene |
RCV001766820 | SCV001991649 | uncertain significance | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV001766820 | SCV002178758 | uncertain significance | not provided | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1547 of the SBF1 protein (p.Arg1547Trp). This variant is present in population databases (rs370182117, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SBF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 811714). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SBF1 protein function with a positive predictive value of 80%. 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. |