Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000693395 | SCV000821263 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2O | 2017-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 3387 of the DYNC1H1 protein (p.Leu3387Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant has been reported to be de novo in an individual affected with DYNC1H1-related disease (Invitae). This variant is not present in population databases (ExAC no frequency). |