ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.380T>C (p.Val127Ala)

gnomAD frequency: 0.00001  dbSNP: rs33925391
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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 RCV001284157 SCV001157504 likely benign not provided 2022-04-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284157 SCV001469784 uncertain significance not provided 2020-09-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001778654 SCV002015004 uncertain significance not specified 2023-12-12 criteria provided, single submitter clinical testing Variant summary: HBB c.380T>C (p.Val127Ala), also known as Hb Beirut, results in a non-conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251316 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.380T>C has been reported in the literature among carriers with normal hematological parameters and normal findings for affinity to bind oxygen and normal stability as determined by the isopropanol test (e.g., Blibech_1986, Strahler_1983). These report(s) do not provide unequivocal conclusions about association of the variant with Hemoglobinopathy. To our knowledge, no quantitative measurements reporting experimental evidence demonstrating an impact on protein function were ascertained. The following publications have been ascertained in the context of this evaluation (PMID: 34272389, 3557996, 26635043, 29790589, 6879181). Two clinical diagnostic laboratories and the OMIM database have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
OMIM RCV000016260 SCV000036528 other HEMOGLOBIN BEIRUT 2017-12-12 no assertion criteria provided literature only

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