Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759073 | SCV000888159 | uncertain significance | not provided | 2017-12-07 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001000143 | SCV001156627 | uncertain significance | not specified | 2019-02-08 | criteria provided, single submitter | clinical testing | The Hb Tende variant (HBB: c.374C>T; p.Pro125Leu, also known as Pro124Leu when numbered from the mature protein, rs33983276) is described as having a normal clinical presentation in heterozygous carriers (see HbVar database, Sangkitporn 2009); however, its phenotype when found with a pathogenic HBB variant on the opposite chromosome is unknown. Functional studies show a moderate increase in oxygen affinity (see HbVar database). A different variant at this codon (Hb Ty Gard: c.374C>A; p.Pro125Gln) is reported with high oxygen affinity and is associated with erythrocytosis (see HbVar database). The Hb Tende variant contains an entry in the ClinVar database (Variation ID: 15569). It is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The proline at codon 125 is highly conserved, but computational analyses (SIFT: Damaging, PolyPhen-2: Benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the Hb Tende variant is uncertain at this time. REFERENCES HbVar link for Hb Tende: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=518&.cgifields=histD HbVar link for Hb Ty Gard: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=516&.cgifields=histD Sangkitporn SK et al. Identification of beta-globin gene mutations in Thailand using an automated fluorescence-based DNA sequencer. Int J Lab Hematol. 2009 Oct;31(5):521-7. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001000143 | SCV001370557 | uncertain significance | not specified | 2020-05-06 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.374C>T (p.Pro125Leu) results in a non-conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. This variant is also known in the literature as "Hemoglobin Tende" or as the legacy name p.Pro124Leu. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251306 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.374C>T has been reported in the literature in at least two asymptomatic carriers with hemoglobin variants (examples- Wajcman_1998, Sangkitporn_2008). These reports 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, indicating that the variant results in a 30-50% increase in oxygen affinity (Wajcman_1998). Two of three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (one submitter did not provide a clinical classification). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000016836 | SCV000037106 | other | HEMOGLOBIN TENDE | 2017-12-12 | no assertion criteria provided | literature only |