ClinVar Miner

Submissions for variant NM_000558.3(HBA1):c.287C>T (p.Pro96Leu)

dbSNP: rs33931314
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506137 SCV000603867 likely pathogenic not specified 2017-01-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000506137 SCV005395265 uncertain significance not specified 2024-09-20 criteria provided, single submitter clinical testing Variant summary: HBA1 c.287C>T (p.Pro96Leu; aka Hb Georgia) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-07 in 1560800 control chromosomes in the gnomAD database (v4.1 dataset). A variant, described as c.287C>T in the alpha-globin gene (the gene, i.e. HBA1 or HBA2, was not specified), has been reported in the literature in an individual affected with hemolytic anemia, however a co-occurring (potentially pathogenic) HBB variant could explain the phenotype (Medri_2022), moreover, a family member, who carried the variant in isolation didn't show signs of hemolysis. The IthaNet database reports the variant c.287C>T in both the HBA1 and HBA2 genes as Benign / Likely Benign (IthaIDs: 3718,683). To our knowledge, no experimental evidence demonstrating an impact on HBA1 protein function has been reported; however, the c.287C>T variant in HBA2 has been reported to result in increased oxygen affinity (PMID 5012316), but no effect on mRNA synthesis (PMID 8745431). The following publication have been ascertained in the context of this evaluation (PMID: 35397565). ClinVar contains an entry for this variant (Variation ID: 15730). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
OMIM RCV000017025 SCV000037297 other HEMOGLOBIN G (GEORGIA) 2016-07-20 no assertion criteria provided literature only

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