Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756240 | SCV000883988 | uncertain significance | not provided | 2021-11-02 | criteria provided, single submitter | clinical testing | The Hb Tyne variant (HBB: c.16C>T; p.Pro6Ser, also known as Pro5Ser when numbered from the mature protein; rs33912272) has been described in the heterozygous state in individuals with normal hematological findings (Pullon 2017, HbVar database and references therein). However, the variant has also been observed in an individual with a clinical diagnosis of beta thalassemia who also carried HbS (Keser 2010). The proline at codon 5 is weakly conserved, and computational programs (PolyPhen-2, SIFT) predict that this variant is tolerated, although isopropanol stability tests indicate this variant is slightly unstable (Pullon 2017, HbVar database). Due to limited information regarding this variant, its clinical significance cannot be determined with certainty. References: Link to HbVar database: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=225 Keser I et al. Abnormal hemoglobins associated with the beta-globin gene in Antalya province, Turkey. Turk J Med Sci. 2010;40(1): 127-131. Pullon BM and Brennan SO. Two familial cases of Hb Tyne confirm instability as cause of low expression. Thalassemia Reports. 2017; 7(1). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000756240 | SCV000889363 | uncertain significance | not provided | 2018-02-02 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271370 | SCV002555968 | uncertain significance | not specified | 2022-06-17 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.16C>T (p.Pro6Ser) results in a non-conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251132 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.16C>T has been reported in the literature in at least one compound heterozygous individual affected with Hemoglobinopathy (Kayisli_2005). The variant was also reported in a severely anemic patient with a truncating variant in cis and a pathogenic splice variant in trans (Agarwal_1997). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: all classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000016806 | SCV000037076 | other | HEMOGLOBIN TYNE | 2017-12-12 | no assertion criteria provided | literature only | |
| Natera, |
RCV001826470 | SCV002091618 | uncertain significance | beta Thalassemia | 2021-04-27 | no assertion criteria provided | clinical testing |