Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814094 | SCV000954492 | uncertain significance | Charcot-Marie-Tooth disease, dominant intermediate B | 2018-09-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 618 of the DNM2 protein (p.Ala618Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs773598203, ExAC 0.01%). This variant has not been reported in the literature in individuals with DNM2-related disease. 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). Variants that disrupt the p.Ala618 amino acid residue in DNM2 have been observed in affected individuals (PMID: 19932619, Invitae). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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. |