Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001061066 | SCV001225793 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2O | 2019-11-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with DYNC1H1-related conditions. 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. 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 C15"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 3629 of the DYNC1H1 protein (p.Phe3629Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. |