Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000686839 | SCV000814376 | uncertain significance | Charcot-Marie-Tooth disease, axonal, type 2O | 2017-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with asparagine at codon 141 of the DYNC1H1 protein (p.Ser141Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs776226690, ExAC 0.03%). This variant has not been reported in the literature in individuals with DYNC1H1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV000719069 | SCV000849933 | likely benign | History of neurodevelopmental disorder | 2020-03-04 | criteria provided, single submitter | clinical testing | Rarity in general population databases (dbsnp, esp, 1000 genomes);Subpopulation frequency in support of benign classification |