ClinVar Miner

Submissions for variant NM_000518.4(HBB):c.232C>T (p.His78Tyr)

dbSNP: rs33991294
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811151 SCV001473254 uncertain significance not provided 2019-07-25 criteria provided, single submitter clinical testing The Hb Fukuyama variant (HBB: c.232C>T; p.His78Tyr, also known as His77Tyr when numbered from the mature protein, rs33991294) is reported in the literature in several heterozygous individuals without clinical symptoms (HbVar database and references therein). This variant is found on a single chromosome (1/251428 alleles) in the Genome Aggregation Database. The histidine at codon 78 is weakly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious, and functional assays suggest the variant is mildly unstable (HbVar database and references therein). However, due to limited information, the clinical significance of the Hb Fukuyama variant is uncertain at this time. References: HbVar link to Hb Fukuyama: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=394
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002281709 SCV002570632 uncertain significance not specified 2022-07-25 criteria provided, single submitter clinical testing Variant summary: HBB c.232C>T (p.His78Tyr) also known as Hb-Fukuyama results in a conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251428 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.232C>T has been reported in the literature as a slightly unstable hemoglobin in reportedly unaffected individuals during routine HbA1c analysis (example, Landin_1993). These report(s) do not provide unequivocal conclusions about association of the variant with Hemoglobinopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
OMIM RCV000016340 SCV000036608 other HEMOGLOBIN FUKUYAMA 2017-12-12 no assertion criteria provided literature only
Natera, Inc. RCV001831569 SCV002089210 uncertain significance beta Thalassemia 2020-07-08 no assertion criteria provided clinical testing

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