Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222352 | SCV002500777 | uncertain significance | not specified | 2022-03-03 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.176C>G (p.Pro59Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251436 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.176C>G has been reported in the literature mainly as part of a complex allele known as Hb Dhofar, which includes the pathogenic variant c.90C>T ( (p.Gly30=) in cis. Hb Dhofar is common in the Sultanate of Oman where it has been reported in multiple compound heterozygous and homozygous individuals affected with Beta Thalassemia (e.g. Daar_2008). The variant c.176C>G in isolation (initially designated as Hb Yukuhashi), has been reported in at least one heterozygous individual in Japan (e.g. Fujita_1972, Darr_2008) and was determined to not differ significantly from hemoglobin A in oxygen affinity, heme-heme interaction, or the Bohr effect. These reports do not provide unequivocal conclusions about association of c.176C>G with Hemoglobinopathy. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, c.176C>G in isolation was classified as uncertain significance until additional evidence of clinical and/or functional importance become available. |
| OMIM | RCV000016651 | SCV000036920 | pathogenic | Hemoglobinopathy | 1968-09-10 | no assertion criteria provided | literature only |