ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.394C>G (p.Gln132Glu) (rs33910209)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281709 SCV000601302 uncertain significance not provided 2020-04-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282942 SCV000883980 likely benign none provided 2019-12-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000507699 SCV000919451 uncertain significance not specified 2018-10-10 criteria provided, single submitter clinical testing Variant summary: HBB c.394C>G (p.Gln132Glu) results in a conservative amino acid change located in the Globin domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 277032 control chromosomes (gnomAD). The variant, c.394C>G, has been reported in the literature in asymptomatic individuals and individuals affected with mild Hemoglobinopathy. These reports do not provide unequivocal conclusions about association of the variant with Hemoglobinopathy. The functional properties of Hb-Camden in the heterozygous state appear to be normal, oxygen affinity appears to be normal, and no abnormalities in haem-haem interaction or Bohr shift was detected (Cohen_1973). However, other variants at this position have been reported as associated with B-thalassemia (c.394C>T, c.394C>A; Ithanet database), suggesting the codon might be important for gene function. To our knowledge, no other experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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