Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000463877 | SCV000546170 | uncertain significance | Jeune thoracic dystrophy | 2017-02-02 | criteria provided, single submitter | clinical testing | This variant has been reported in individuals affected with asphyxiating thoracic dystrophy (ATD) (PMID: 23339108, 23456818) and has been shown to segregate with ATD in a single family (Invitae). This sequence change replaces isoleucine with methionine at codon 2819 of the DYNC2H1 protein (p.Ile2819Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Revvity Omics, |
RCV003144267 | SCV003830789 | uncertain significance | Asphyxiating thoracic dystrophy 3 | 2021-04-23 | criteria provided, single submitter | clinical testing |