Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000228142 | SCV000287114 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2O | 2023-12-03 | 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 1191 of the DYNC1H1 protein (p.Arg1191Cys). This variant is present in population databases (rs774198261, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 238999). 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 with a positive predictive value of 95%. 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 |
RCV000236103 | SCV000294178 | uncertain significance | not provided | 2019-04-08 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002516315 | SCV003745378 | uncertain significance | Inborn genetic diseases | 2022-11-21 | criteria provided, single submitter | clinical testing | The c.3571C>T (p.R1191C) alteration is located in exon 16 (coding exon 16) of the DYNC1H1 gene. This alteration results from a C to T substitution at nucleotide position 3571, causing the arginine (R) at amino acid position 1191 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |