Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985737 | SCV001134213 | likely pathogenic | not provided | 2022-09-18 | criteria provided, single submitter | clinical testing | It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, individuals heterozygous for this variant present with chronic mild hemolytic anemia (PMID: 35898763 (2022), 7928379 (1994), 3583764 (1987), 5791730 (1969)). In a functional study, this variant exhibited minor alterations in function in an assay that evaluated oxidation and reduction rates (PMID: 7407240 (1980)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as likely pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586013 | SCV005076102 | uncertain significance | not specified | 2024-04-16 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.199A>G (p.Lys67Glu) results in a conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251432 control chromosomes. c.199A>G has been reported in the literature as a heterozygous genotype in settings of mild chronic hemolytic anemia with unstable hemoglobin and increased methemoglobin levels (cited in Xu_2022, Rosa_1969), and low oxygen saturations (Xu_2022). It has also been reported as a compound heterozygous genotype with HbS in at-least one individual with joint pain and hemolytic anemia (Tejuca_1987) and in settings of a co-existing diagnosis of alpha thallasemia (example, Hendy_1994, Pullon_2016). These data indicate that the variant may be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 7928379, 5791730, 3583764, NO_PMID for Pullon_2016). ClinVar contains an entry for this variant (Variation ID: 15206). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV000016390 | SCV000036658 | pathogenic | Hemoglobinopathy | 1971-04-27 | no assertion criteria provided | literature only |