Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000821993 | SCV000962770 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 1487 of the SBF2 protein (p.Pro1487Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SBF2-related conditions. 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"). 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. |
Molecular Genetics Laboratory, |
RCV001173105 | SCV001336181 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
ARUP Laboratories, |
RCV001803993 | SCV002048760 | uncertain significance | Charcot-Marie-Tooth disease type 4B2 | 2021-01-12 | criteria provided, single submitter | clinical testing | The SBF2 c.4459C>T; p.Pro1487Ser variant (rs1590103742), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 663998).This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The proline at codon 1487 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.95). Due to limited information, the clinical significance of the p.Pro1487Ser variant is uncertain at this time. |