Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705097 | SCV000834078 | uncertain significance | Charcot-Marie-Tooth disease, type 2 | 2018-09-04 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with asparagine at codon 470 of the AARS protein (p.Ile470Asn). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with hereditary motor and sensory polyneuropathy type 2 (PMID: 27164712). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Molecular Genetics Laboratory, |
RCV000999708 | SCV001156494 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |