Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414412 | SCV000491791 | likely pathogenic | not provided | 2016-11-11 | criteria provided, single submitter | clinical testing | The R1962H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species, and different missense variants in the same residue (R1962C, R1962L) have been reported in the Human Gene Mutation Database in association with DYNC1H1-related disorders (Stenson et al., 2014). In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R1962H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Fulgent Genetics, |
RCV000762920 | SCV000893335 | likely pathogenic | Spinal muscular atrophy, lower extremity predominant 1, autosomal dominant; Charcot-Marie-Tooth disease, axonal, type 2O; Mental retardation, autosomal dominant 13 | 2018-10-31 | criteria provided, single submitter | clinical testing |