Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000535636 | SCV000657962 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2019-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 1374 of the SBF2 protein (p.Leu1374Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs746286799, ExAC 0.02%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with SBF2-related disease. 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: "Tolerated"; PolyPhen-2: "Possibly 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. |