Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001049861 | SCV001213935 | uncertain significance | Usher syndrome type 3B | 2021-03-23 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with HARS-related conditions. This variant is present in population databases (rs769535360, ExAC 0.06%). This sequence change replaces glycine with arginine at codon 219 of the HARS protein (p.Gly219Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |