ClinVar

Description

Variant summary: HBB c.420T>G (p.Asn140Lys) results in a non-conservative amino acid change in 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 251376 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.420T>G (Hb-Hinsdale) has been reported in the literature in individuals affected with mild anemia (examples: Moo-Penn_1989 and Degani_2001). These report(s) do not provide unequivocal conclusions about association of the variant with Hemoglobinopathy. Multiple publications have reported experimental evidence evaluating an impact on protein function, one study reported this variant did not affect HbS gelation (Watowich_1989) and a seperate study showed the variant mildly reduced oxygen affinity (Moo-Penn_1989). The following publications have been ascertained in the context of this evaluation (PMID: 2513289, 2585512, 11317140). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.