Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000016485 | SCV001360652 | uncertain significance | not specified | 2019-11-01 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.8A>C (p.His3Pro), also known as Hb Long Island-Marseille and Hb Agrigente in the literature and variant databases, results in a non-conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251140 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8A>C has been reported in the literature as an abnormal hemoglobin detected during HbA1C evaluation in diabetic patients who were otherwise hematologically normal (Barwick_1985, Blouquit_1984, Boi_1989, Wei_2019). These reports do not provide unequivocal conclusions about association of the variant with Hemoglobinopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 until additional clinical and functional evidence becomes available. |
| OMIM | RCV000016485 | SCV000036752 | pathogenic | not specified | 1989-01-01 | no assertion criteria provided | literature only |