ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.123G>T (p.Arg41Ser)

gnomAD frequency: 0.00001  dbSNP: rs33918778
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281733 SCV000601239 uncertain significance not provided 2024-04-24 criteria provided, single submitter clinical testing The HBB c.123G>T (p.Arg41Ser) variant (also known as Hb Austin) has been reported in the published literature to have normal stability and increased oxygen affinity, and individuals heterozygous for this variant have a normal clinical presentation (HbVar (http://globin.cse.psu.edu/cgi-bin/hbvar/counter) and PMID: 24878022 (2014)). 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 damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001281733 SCV000883984 uncertain significance not provided 2023-11-20 criteria provided, single submitter clinical testing The Hb Austin variant (HBB: c.123G>T; p.Arg41Ser, also known as Arg40Ser when numbered from the mature protein, rs33918778, HbVar ID: 311) is reported in the literature in the heterozygous state in multiple individuals of Mexican ancestry with no clinical symptoms (HbVar and references therein, Racsa 2014, Moo-Penn 1977). However, the phenotype of this variant in the presence of other alpha globin variants is unknown. Functional characterization indicate that the variant hemoglobin has normal Bohr effect, increased oxygen affinity, reduced cooperativity, and found to dissociate into oxyHb dimers (HbVar and references therein). The c.123G>T variant is reported in ClinVar (Variation ID: 439134). It is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.9). Due to the limited information regarding this variant, its clinical significance is uncertain at this time. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Racsa LD et al. Beta-Globin gene sequencing of hemoglobin Austin revises the historically reported electrophoretic migration pattern. Arch Pathol Lab Med. 2014 Jun;138(6):819-22. PMID: 24878022. Moo-Penn WF et al. Hemoglobins Austin and Waco: two hemoglobins with substitutions in the alpha 1 beta 2 contact region. Arch Biochem Biophys. 1977 Feb;179(1):86-94. doi: 10.1016/0003-9861(77)90089-3. PMID: 14597.
Fulgent Genetics, Fulgent Genetics RCV002490848 SCV002780466 uncertain significance Dominant beta-thalassemia; Heinz body anemia; Hb SS disease; alpha Thalassemia; Malaria, susceptibility to; METHEMOGLOBINEMIA, BETA TYPE; Erythrocytosis, familial, 6; Hereditary persistence of fetal hemoglobin; Beta-thalassemia HBB/LCRB 2021-12-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV001272128 SCV001453781 uncertain significance beta Thalassemia 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.