Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000755549 | SCV000601266 | likely benign | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000755549 | SCV000603949 | likely benign | not provided | 2023-10-30 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000506157 | SCV000917491 | likely benign | not specified | 2022-10-05 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.286A>G (p.Lys96Glu) also known as Hb-N Baltimore, results in a conservative amino acid change located in the Globin domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.4e-05 in 277156 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. Multiple publications cite the variant with in asymptomatic and mildly affected individuals with normal hematological parameters characteristic of alpha thal-trait (in settings of -alpha/-alpha genotype) or a beta-thal trait (in setting of Hb-N-Baltimore/beta-thal) (Johnson_1976, Adams_1977, Ballas_1985, Hirsch_1997, Huisman_1997). A case study by Farashi_2016 reports the variant to occur in cis with HBB c.272_295dup (a duplication of eight codons) in a mother and daughter with relatively normal hematological parameters, however, authors speculate that the variant of interest could also influence structural changes. Functional studies showed that this variant significantly accelerated the crystallization of HbC (Hirsch_1997), inhibited gelation of HbS in deoxy state while behaving like HbA in oxy state (Kumpati_1978) and was associated with normal oxygen affinity (Craescu_1988). Furthermore, the variant showed poor reducibility of oxidized hemoglobin and impairment in interaction with cytochrome b5 (Gacon_1980). However, the impact of these findings on the pathophysiology of hemoglobinopathies is unclear. This variant is widely regarded as an apparently harmless or a clinically benign hemoglobin in the literature spanning over 3 decades (example, Schneider_1976, Mason_2016). Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Revvity Omics, |
RCV000755549 | SCV004235258 | uncertain significance | not provided | 2023-06-26 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000016504 | SCV000036772 | other | HEMOGLOBIN N (BALTIMORE) | 2017-12-12 | no assertion criteria provided | literature only | |
| OMIM | RCV000016505 | SCV000036773 | other | HEMOGLOBIN N (JENKINS) | 2017-12-12 | no assertion criteria provided | literature only | |
| OMIM | RCV000016506 | SCV000036774 | other | HEMOGLOBIN JENKINS | 2017-12-12 | no assertion criteria provided | literature only | |
| OMIM | RCV000016507 | SCV000036775 | other | HEMOGLOBIN HOPKINS 1 | 2017-12-12 | no assertion criteria provided | literature only | |
| OMIM | RCV000016508 | SCV000036776 | other | HEMOGLOBIN KENWOOD | 2017-12-12 | no assertion criteria provided | literature only | |
| Natera, |
RCV001835628 | SCV002089201 | likely benign | beta Thalassemia | 2020-09-23 | no assertion criteria provided | clinical testing |