Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759797 | SCV000889369 | uncertain significance | not provided | 2021-06-18 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000759797 | SCV001156628 | uncertain significance | not provided | 2022-06-07 | criteria provided, single submitter | clinical testing | The Hb Hofu variant (HBB: c.380T>A; p.Val127Glu, also known as Val126Glu when numbered from the mature protein, rs33925391, HbVar ID: 519) is reported in the literature in the heterozygous state in both individuals with mild anemia and asymptomatic individuals (Purohit 2014, HbVar database and references therein). This variant was also reported in an individual with thalassemia intermedia who also carried a beta-0 variant (Pande 1995), though it has been described in trans to Hb S in both symptomatic and asymptomatic individuals (Huisman 1997, Purohit 2014, HbVar database). Hematological measurements in carriers indicate that Hb Hofu is a mildly unstable variant (Huisman 1997, Purohit 2014, HbVar database). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The valine at codon 127 is moderately conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.646). Based on available 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 Huisman TH et al. Combinations of beta chain abnormal hemoglobins with each other or with beta-thalassemia determinants with known mutations: influence on phenotype. Clin Chem. 1997 Oct;43(10):1850-6. PMID: 9342003 Pande PL et al. Beta-thalassemia intermedia in an Indian female with the Hb Hofu (beta 126(H4)Val-->Glu)-beta zero-thalassemia (codons 8/9 (+G)) combination. Hemoglobin. 1995 Sep;19(5):301-6. PMID: 8537236 Purohit P et al. Clinical and molecular characterization of Hb Hofu in eastern India. Int J Lab Hematol. 2014 Feb;36(1):71-6. PMID: 23889802 |
| Neuberg Centre For Genomic Medicine, |
RCV001507092 | SCV001712067 | likely pathogenic | beta Thalassemia | criteria provided, single submitter | clinical testing | The missense variant NM_000518.5(HBB):c.380T>A (p.Val127Glu) has been previously reported as Hb Hofu and has been observed in Indian population (Pande et al, Purohit et al, Warghade et al). It has been submitted to ClinVar with conflicting interpretations of pathogenicity : VUS/Likely Pathogenic. In combination with a beta 0 variant it has been reported with a thalssemia intermedia phenotype and has been observed in asymptomatic as well as symptomatic indviduals in trans with sickle cell trait (Arends T et al,Brittenham G et al, Purohit et al). The p.Val127Glu variant is novel (not in any individuals) in gnomAD. The p.Val127Glu variant is novel (not in any individuals) in 1kG. There is a moderate physicochemical difference between valine and glutamic acid. In silico tools predict a damaging effect while the residue is weakly conserved across species. For these reasons, this variant has been classified as Likely Pathogenic. | |
| OMIM | RCV000016384 | SCV000036652 | other | HEMOGLOBIN HOFU | 2017-12-12 | no assertion criteria provided | literature only | |
| Molecular Genetics Laboratory, |
RCV001507092 | SCV004244255 | pathogenic | beta Thalassemia | 2023-10-27 | no assertion criteria provided | clinical testing |