Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001340350 | SCV001534156 | uncertain significance | Giant axonal neuropathy 1 | 2022-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 261 of the GAN protein (p.Ala261Val). This variant is present in population databases (rs574374537, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GAN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1037226). 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: "Benign"; Align-GVGD: "Class C55"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| ARUP Laboratories, |
RCV001340350 | SCV002048005 | uncertain significance | Giant axonal neuropathy 1 | 2020-12-16 | criteria provided, single submitter | clinical testing | The GAN c.782C>T; p.Ala261Val variant (rs574374537), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on nine chromosomes (9/282858 alleles) in the Genome Aggregation Database. The alanine at codon 261 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.362). However, given the lack of clinical and functional data, the significance of the p.Ala261Val variant is uncertain at this time. |