Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004767011 | SCV005381110 | uncertain significance | not specified | 2024-08-14 | criteria provided, single submitter | clinical testing | Variant summary: HBA2 c.310C>T (p.His104Tyr) results in a conservative amino acid change located in the globin domain (IPR000971) of 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 248064 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.310C>T has been reported in the literature in the heterozygous state in individuals with mild anemia (e.g. Guida_2006, Hoyer_2002, Lucan_1999). These report(s) do not provide unequivocal conclusions about association of the variant with Alpha Thalassemia. At least one publication reports experimental evidence that this variant inhibits binding to Beta globin and AHSP, however, does not allow convincing conclusions about the variant effect (e.g. Yu_2009). This variant is also known as Hb Lombard, Hb Charolles, and H103Y. The following publications have been ascertained in the context of this evaluation (PMID: 16503552, 12144061, 10569723, 19349619). ClinVar contains an entry for this variant (Variation ID: 15673). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000016959 | SCV000037231 | other | HEMOGLOBIN LOMBARD | 2013-03-28 | no assertion criteria provided | literature only |