Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757190 | SCV000885328 | uncertain significance | not provided | 2017-06-02 | criteria provided, single submitter | clinical testing | The p.Arg1542Gly variant has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. It is also absent from population databases such as 1000 Genomes, the NHLBI GO Exome Sequencing Project (ESP), and the Genome Aggregation Database (gnomAD) browser. The arginine at codon 1542 is highly conserved considering 11 species up to C. elegans (Alamut software v2.8.1), and computational analyses suggest this variant has a significant effect on DYNC1H1 protein structure/function (SIFT: damaging, PolyPhen2: probably damaging, and Mutation Taster: disease causing). However, based on the available information, the clinical significance of the p.Arg1542Gly variant cannot be determined with certainty. |
| Invitae | RCV003642915 | SCV004487890 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2O | 2022-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1542 of the DYNC1H1 protein (p.Arg1542Gly). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DYNC1H1 protein function. ClinVar contains an entry for this variant (Variation ID: 618610). This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. |