Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001223460 | SCV001395612 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 18 of the FIG4 protein (p.Tyr18Cys). This variant is present in population databases (rs762687855, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 951520). 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: "Probably 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. 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. |
Ambry Genetics | RCV002348749 | SCV002651452 | uncertain significance | Inborn genetic diseases | 2020-03-24 | criteria provided, single submitter | clinical testing | The p.Y18C variant (also known as c.53A>G), located in coding exon 1 of the FIG4 gene, results from an A to G substitution at nucleotide position 53. The tyrosine at codon 18 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |