Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759776 | SCV000889340 | uncertain significance | not provided | 2023-05-27 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in individuals with normal hematological characterizations (PMID: 5870555 (1965), 5169069 (1971)), as well as individuals with diabetes (PMID: 25109349 (2014)), and individuals with hypochromic microcytic anemia (PMID: 23402770 (2013)). This variant is reported as having normal stability and normal cell morphology (PMID: 5870555 (1965), 5169069 (1971)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| ARUP Laboratories, |
RCV000759776 | SCV001160067 | uncertain significance | not provided | 2022-08-16 | criteria provided, single submitter | clinical testing | The Hb J Toronto variant (HBA1 c.17C>A; p.Ala6Asp, also known as or Ala5Asp when numbered from the mature protein, rs34090856, HbVarID: 3) is reported in the literature in the heterozygous state and in the compound heterozygous state with the 3.7kb deletion in individuals without any significant hematological symptoms (see HbVar and references therein, Mahdavi 2012, Van Laer 2014). Aberrant HbA1c measurements have been reported in several individuals with this variant (Van Laer 2014). This variant is reported in ClinVar (Variation ID: 15765), and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The alanine at codon 6 is weakly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.544). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Mahdavi M et al. Report of haemoglobin J-Toronto and alpha thalassemia in a family from North of Iran. J Pak Med Assoc. 2012 Apr;62(4):396-8. PMID: 22755290. Van Laer C et al. Aberrant glycated haemoglobin (HbA1c) results leading to haemoglobinopathy diagnosis in four Belgian patients. Acta Clin Belg. 2014 Dec;69(6):456-9. PMID: 25109349. |
| OMIM | RCV000017076 | SCV000037348 | other | HEMOGLOBIN J (TORONTO) | 2016-07-20 | no assertion criteria provided | literature only | |
| Natera, |
RCV001831578 | SCV002093858 | uncertain significance | alpha Thalassemia | 2021-08-31 | no assertion criteria provided | clinical testing |