Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001230225 | SCV001402699 | uncertain significance | Usher syndrome type 3B | 2023-06-21 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HARS protein function. ClinVar contains an entry for this variant (Variation ID: 957273). This variant has not been reported in the literature in individuals affected with HARS-related conditions. This variant is present in population databases (rs138035024, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 149 of the HARS protein (p.Arg149Cys). |
| Ambry Genetics | RCV002462852 | SCV002754643 | uncertain significance | Inborn genetic diseases | 2020-07-28 | criteria provided, single submitter | clinical testing | The p.R149C variant (also known as c.445C>T), located in coding exon 5 of the HARS gene, results from a C to T substitution at nucleotide position 445. The arginine at codon 149 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |