Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000792475 | SCV000357241 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate C | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000792475 | SCV000931777 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate C | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 292 of the YARS protein (p.Tyr292Asp). This variant is present in population databases (rs753211165, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with YARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 297155). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on YARS protein function. 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. |
| Athena Diagnostics | RCV000993560 | SCV001146660 | uncertain significance | not provided | 2019-08-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000993560 | SCV002599871 | uncertain significance | not provided | 2022-05-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 16429158) |
| 3billion | RCV004725153 | SCV005328612 | likely benign | Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 | 2024-09-20 | criteria provided, single submitter | clinical testing | The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. |