Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV001591166 | SCV000613377 | uncertain significance | not provided | 2021-04-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000653904 | SCV000775794 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-06-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 391 of the GARS protein (p.Arg391Cys). This variant is present in population databases (rs370057212, gnomAD 0.003%). This missense change has been observed in individual(s) with Charcot Marie Tooth disease (PMID: 24078732). ClinVar contains an entry for this variant (Variation ID: 447371). 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. |
Gene |
RCV001591166 | SCV001826166 | likely benign | not provided | 2020-12-22 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 26752306, 24078732) |
Ambry Genetics | RCV002461270 | SCV002755184 | uncertain significance | Inborn genetic diseases | 2021-05-04 | criteria provided, single submitter | clinical testing | The p.R391C variant (also known as c.1171C>T), located in coding exon 9 of the GARS gene, results from a C to T substitution at nucleotide position 1171. The arginine at codon 391 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was detected in an individual with Charcot-Marie-Tooth (CMT) disease, and in an unaffected control individual in a different CMT disease cohort; however, clinical details were limited (Sivera R et al. Neurology, 2013 Oct;81:1617-25; Lupo V et al. J Mol Diagn, 2016 Mar;18:225-34). 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. |
Inherited Neuropathy Consortium | RCV000789778 | SCV000929162 | likely benign | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
Genesis Genome Database | RCV000789778 | SCV000999758 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research | |
Inherited Neuropathy Consortium Ii, |
RCV003447142 | SCV004174567 | uncertain significance | Charcot-Marie-Tooth disease type 2D | 2016-01-06 | no assertion criteria provided | literature only |