Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000699267 | SCV000827969 | uncertain significance | Usher syndrome type 3B | 2019-05-29 | criteria provided, single submitter | clinical testing | 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 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with HARS-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 204 of the HARS protein (p.Ile204Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. |
| Ambry Genetics | RCV002462042 | SCV002755236 | uncertain significance | Inborn genetic diseases | 2019-08-30 | criteria provided, single submitter | clinical testing | The p.I204M variant (also known as c.612A>G), located in coding exon 6 of the HARS gene, results from an A to G substitution at nucleotide position 612. The isoleucine at codon 204 is replaced by methionine, an amino acid with highly similar properties. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |