Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586865 | SCV000697086 | uncertain significance | not specified | 2020-07-07 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.151A>T (p.Thr51Ser) results in a conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251426 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.151A>T has been reported in the literature in a hematologically asymptomatic individual (Kleinert_2008) and among the abnormal hemoglobin variants identified in a thalassemia screening cohort study (example, Zhang_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. One internal specimen analyzed at our laboratory carried this variant in addition to two other pathogenic HBB variants (c.316-197C>T, and c.79G>A, HbE), however, the phase of this variant was not analyzed. This finding is suggestive of an unlikely association with disease. No other 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 VUS-possibly benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478322 | SCV004219860 | uncertain significance | not provided | 2022-11-15 | criteria provided, single submitter | clinical testing | The HBB c.151A>T (p.Thr51Ser) variant, also known as Hb Zurich-Langstrasse, is described as having normal stability. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in a heterozygous asymptomatic individual (PMID: 17932132 (2008)). Additionally, the variant has been identified in individuals and neonates during large beta thalassemia screening studies in the Chinese population (PMIDs: 30809867 (2019) and 33439495 (2021)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Taking into account the available information, we are unable to determine the clinical significance of this variant. |
Natera, |
RCV001272127 | SCV001453780 | uncertain significance | beta Thalassemia | 2020-09-16 | no assertion criteria provided | clinical testing |