Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000506716 | SCV000603922 | uncertain significance | not specified | 2018-10-11 | criteria provided, single submitter | clinical testing | The Hb Summer Hill variant (c.157G>C, Asp52His) has been observed in a sample submitted for thalassemia/hemoglobinopathy screening (Turner 2016), but it is reported to be functionally equivalent to Hb A and is not associated with significant clinical symptoms (HbVar database and references therein). However, its phenotype when found with other globin variants is unknown. It is listed in the dbSNP variant database (rs33961886), but not observed in the general population databases (1000 Genomes Project, Exome Variant Server, Exome Aggregation Consortium). The aspartate at residue 52 is weakly conserved, but computational algorithms (Align GVGD, Mutation Taster, PolyPhen-2, SIFT) are inconclusive on the variant's impact on the protein. Due to the limited information regarding this variant, its clinical significance is uncertain. References: Link to HbVar database for Hb Summer Hill: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=336 Turner A et al. Rapid detection of pathological mutations and deletions of the haemoglobin beta gene (HBB) by High Resolution Melting (HRM) analysis and Gene Ratio Analysis Copy Enumeration PCR (GRACE-PCR). BMC Med Genet. 2016 Oct 19;17(1):75. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284630 | SCV001470517 | uncertain significance | not provided | 2020-08-06 | criteria provided, single submitter | clinical testing | The HBB c.157G>C (p.Asp53His) variant, also known as Hb Summer Hill, has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant was found in a Lebanese woman (PMID: 7190137 (1980)) and in a Turkish family from Cyprus with no hematological abnormalities (PMID: 6629828 (1983)). This variant has been described as rare beta-chain variant (PMID: 26635043 (2016)). 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. Based on the available information, we are unable to determine the clinical significance of this variant. |
| OMIM | RCV000016613 | SCV000036882 | other | HEMOGLOBIN SUMMER HILL | 2017-12-12 | no assertion criteria provided | literature only | |
| Natera, |
RCV001826468 | SCV002089219 | uncertain significance | beta Thalassemia | 2021-04-09 | no assertion criteria provided | clinical testing |