Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Clinical Services Laboratory, |
RCV001094399 | SCV000398675 | uncertain significance | Charcot-Marie-Tooth disease, type 2N | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV000653852 | SCV000775742 | uncertain significance | Charcot-Marie-Tooth disease, type 2 | 2017-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 418 of the AARS protein (p.Tyr418Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs147433234, ExAC 0.04%). This variant has not been reported in the literature in individuals with AARS-related disease. ClinVar contains an entry for this variant (Variation ID: 320344). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. 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, |
RCV000999706 | SCV001156492 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |