Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001804737 | SCV002051427 | uncertain significance | not specified | 2021-12-30 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.149C>T (p.Ser50Phe), also known as Hemoglobin Las Palmas 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 251424 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.149C>T has been reported in the literature as a mildly unstable variant in carrier individuals from Canary Islands with relatively normal hematological parameters (example, Malcorra-Azpiazu_1988) and also as a frequent cause for falsely abnormal HbA1c measurement among diabetic patient carriers living in the Canary Islands (example, Lorenzo-Medina_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Hemoglobinopathy. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in a mildly unstable hemoglobin based on heat denaturation and isopropanaol tests (example, Malcorra-Azpiazu_1988). No clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003476894 | SCV004219859 | uncertain significance | not provided | 2023-07-25 | criteria provided, single submitter | clinical testing | The HBB c.149C>T (p.Ser50Phe) variant (also known as Hb Las Palmas) has been reported in the published literature in two healthy family members and was described as mildly unstable (PMID: 3384708 (1988)). This variant did not affect hematological values, though there was a slightly elevated reticulocyte count (PMID: 3384708 (1988)). The frequency of this variant in the general population, 0.0000066 (1/152122 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| OMIM | RCV000016451 | SCV000036719 | other | HEMOGLOBIN LAS PALMAS | 2017-12-12 | no assertion criteria provided | literature only |