Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519658 | SCV000617391 | likely pathogenic | not provided | 2017-11-02 | criteria provided, single submitter | clinical testing | The F141L variant was initially reported in the hemizygous state in an individual with Charcot-Marie-Tooth disease (CMT) (Rouger et al., 1997). Subsequently, F141L was reported in additional families with CMT, although detailed clinical information and segregation analysis was not provided (Birouk et al., 1998; Dubourg et al., 2001). The F141L variant is not observed in large population cohorts (Lek et al., 2016). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and missense variants in nearby residues (V139M; R142Q/W) have been reported in the Human Gene Mutation Database in association with CMT (Stenson et al., 2014), supporting the functional importance of this region of the protein. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. |
Inherited Neuropathy Consortium | RCV000789935 | SCV000929320 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |