Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004690867 | SCV005184374 | likely pathogenic | beta Thalassemia | 2024-05-01 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.327C>G (p.Asn109Lys) 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 was absent in 251212 control chromosomes. c.327C>G has been reported in the literature in one individual affected with Beta Thalassemia in the compound heterozygous state (Schnee_1990). Experimental studies show that this variant abolishes the MaeII recognition site and mice homozygous for this variant have hemolytic anemia and erythrocytes with a shortened lifespan (e.g. Schnee_1990, Suzuki_2002, Izumizaki_2003). This variant is also known as Hb Presbyterian. The following publications have been ascertained in the context of this evaluation (PMID: 12829441, 2307460, 12127975).ClinVar contains an entry for this variant (Variation ID: 15318). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV005000574 | SCV005625766 | likely pathogenic | not provided | 2024-06-14 | criteria provided, single submitter | clinical testing | The HBB c.327C>G (p.Asn109Lys) variant has been reported in the published literature in individuals with mild anemia (PMIDs: 668922 (1978), 500379 (1979), 3101357 (1986), anemia (PMID: 6309649 (1983)), and hypochromic microcytic anemia (PMID: 28395541 (2017)). Functional studies have demonstrated a decreased oxygen affinity and decreased stability (PMIDs: 12458204 (2003) and 12127975 (2002)). However, heterozygotes may have no hematologic abnormalities (PMID: 12127975 (2002)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). 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, this variant is classified as likely pathogenic. |
| Fulgent Genetics, |
RCV005051468 | SCV005684689 | likely pathogenic | Dominant beta-thalassemia; Heinz body anemia; Hb SS disease; Malaria, susceptibility to; METHEMOGLOBINEMIA, BETA TYPE; Erythrocytosis, familial, 6; Hereditary persistence of fetal hemoglobin; Beta-thalassemia HBB/LCRB | 2024-05-04 | criteria provided, single submitter | clinical testing |