Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001239587 | SCV001412470 | uncertain significance | Giant axonal neuropathy 1 | 2019-11-16 | criteria provided, single submitter | clinical testing | 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 tolerated, 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with GAN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with aspartic acid at codon 143 of the GAN protein (p.His143Asp). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and aspartic acid. |