Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Hudson |
RCV000033152 | SCV000537217 | uncertain significance | Autosomal dominant Charcot-Marie-Tooth disease type 2W | 2024-01-04 | criteria provided, single submitter | research | |
Center for Pediatric Genomic Medicine, |
RCV000514458 | SCV000609999 | uncertain significance | not provided | 2017-08-30 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000650143 | SCV000771980 | uncertain significance | Usher syndrome type 3B | 2024-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 137 of the HARS protein (p.Arg137Gln). This variant is present in population databases (rs191391414, gnomAD 0.02%). This missense change has been observed in individual(s) with HARS-related conditions (PMID: 22930593, 27353947, 29790872, 36964972). This variant is also known as c.290G>A (p.Arg97Gln). ClinVar contains an entry for this variant (Variation ID: 40062). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt HARS protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects HARS function (PMID: 22930593, 32543048). 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. |
Gene |
RCV000514458 | SCV001785908 | uncertain significance | not provided | 2022-10-04 | criteria provided, single submitter | clinical testing | Reported as a heterozygous variant in an individual with peripheral neuropathy (Vester et al., 2013); Reported with a variant on the opposite allele (in trans) in a patient with Usher syndrome in published literature (Tiwari et al., 2016); Published functional studies demonstrate the R137Q variant reduces neurite outgrowth as a result of decreased protein synthesis (Mullen et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23465884, 26072516, 29790872, 27353947, 33236345, 24917879, 23913540, 27876679, 32940403, 22930593, 29288497, 32372680, 32543048) |
Mendelics | RCV002247415 | SCV002517167 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002247415 | SCV002755246 | uncertain significance | not specified | 2023-06-05 | criteria provided, single submitter | clinical testing | The c.410G>A (p.R137Q) alteration is located in exon 5 (coding exon 5) of the HARS gene. This alteration results from a G to A substitution at nucleotide position 410, causing the arginine (R) at amino acid position 137 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
OMIM | RCV000033152 | SCV000056934 | pathogenic | Autosomal dominant Charcot-Marie-Tooth disease type 2W | 2013-01-01 | flagged submission | literature only | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000514458 | SCV001979554 | uncertain significance | not provided | 2024-01-02 | no assertion criteria provided | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000514458 | SCV001979964 | likely pathogenic | not provided | flagged submission | clinical testing | ||
Clinical Genetics, |
RCV000514458 | SCV002034354 | likely pathogenic | not provided | flagged submission | clinical testing |