Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000589411 | SCV000603917 | likely benign | not provided | 2024-06-09 | criteria provided, single submitter | clinical testing | The Hb D-Iran variant (HBB: c.67G>C; p.Glu23Gln, also known as Glu22Gln when numbered from the mature protein, HbVarID: 267, rs33959855) has been reported in individuals with no associated hematological symptoms (Rahbar 1973, HbVar database and references therein), and did not affect clinical symptoms when occurring in-trans with beta-0 thalassemia alleles (Rohe 1973, Agrawal 2007). Functional characterizations indicate that the variant hemoglobin exhibits normal oxygen affinity, Bohr effect and cooperative interactions (Rohe 1973). The variant is listed in ClinVar (Variation ID: 15151). This variant observed in the South Asian population with an allele frequency of 0.05% (15/30614 alleles) in the Genome Aggregation Database. The glutamic acid at codon 23 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.54). Based on available information, this variant is considered to be likely benign. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Agrawal MG et al. Compound heterozygosity of Hb D(Iran) (beta(22) Glu-->Gln) and beta(0)-thalassemia (619 bp-deletion) in India. Eur J Haematol. 2007 Sep;79(3):248-50. PMID: 17655708. Rahbar S. Haemoglobin D Iran: 2 22 glutamic acid leads to glutamine (B4). Br J Haematol. 1973 Jan;24(1):31-5. PMID: 4715135. Rohe RA et al. Hemoglobin D Iran alpha A2 beta 22 2-Glu leads to Gln in association with thalassemia. Blood. 1973 Sep;42(3):455-62. PMID: 4725603. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001280542 | SCV000697142 | uncertain significance | not specified | 2025-04-15 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.67G>C (p.Glu23Gln) results in a conservative amino acid change located in the globin domain (IPR000971) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251278 control chromosomes, predominantly at a frequency of 0.00049 within the South Asian subpopulation in the gnomAD database. This frequency is not higher than estimated for a pathogenic variant in HBB causing Beta Thalassemia (6e-05 vs 0.011), allowing no conclusion about variant significance. Hb D-Iran was identified in compound heterozygosity with Hb A with an asymptomatic clinical course, normal hemoglobin concentration, normal red blood cell morphology, absence of inclusion bodies, and a normal level of methemoglobin (Rahbar_1973). Hb D-Iran in combination with HbS causes benign sickle syndrome with normal red cell indices, normal growth, and no evidence of hemolysis or organomegaly (Serjeant_1982). A compound heterozygote for Hb D-Iran and - thal presented with hypochromic microcytic anemia with target cells and basophilic stippling with these finding being no different from those of a - thal carriers alone (Rohe_1973, Agrawal_2007, Bhat_2012, Mohanty_2017). Thornburg_2001 concluded that homozygous Hb D-Iran is a relatively benign condition with mild microcytic anemia, poikilocytosis, and minimal hemolysis based on the hematologic values, hemoglobin electrophoresis, peripheral blood smear, and clinical course. Hb D-Iran has no reported abnormalities in heat stability, oxygen equilibrium, intracellular 2,3 DPG, Bohr effect, or heme-heme interaction (Rohe_1973). The following publications have been ascertained in the context of this evaluation (PMID: 35287566, 17655708, 19783722, 23543793, 27207683, 8195010, 25332633, 9342003, 29519374, 33279152, 4715135, 4725603, 20090224, 20838957, 31553106, 7073867, 11196276, 20309827). ClinVar contains an entry for this variant (Variation ID: 15151). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000589411 | SCV000889377 | likely benign | not provided | 2023-04-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000589411 | SCV002558068 | uncertain significance | not provided | 2022-07-21 | criteria provided, single submitter | clinical testing | Reported in the homozygous and compound heterozygous state in patients with mild hemoglobinopathy (Thornburg et al., 2001; Bhat et al., 2012; Gupta et al., 2014); Also known as Hb D-Iran and p.E22Q; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20090224, 4715135, 8195010, 6434492, 7073867, 25023086, 20838957, 19783722, 4725603, 11196276, 17655708, 31553106, 20309827, 23543793, 25332633, 19429541) |
| OMIM | RCV000016314 | SCV000036582 | other | HEMOGLOBIN D (IRAN) | 2017-12-12 | no assertion criteria provided | literature only |