ClinVar Miner

Submissions for variant NM_000517.6(HBA2):c.379G>A (p.Asp127Asn) (rs33933481)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000609 SCV001157598 pathogenic none provided 2020-08-20 criteria provided, single submitter clinical testing The Hb Tarrant variant (HBA2: c.379G>A; p.Asp127Asn, also known as Asp126Asn when numbered from the mature protein) has been described in healthy individuals or individuals with mild erythrocytosis as a heterozygote and more severe erythrocytosis as a homozygote (Ibarra 1981, Ip 2016, HbVar database). The aspartate at residue 127 is located at the alpha1-alpha2 interface and forms salt bridges with Arg142 on the opposite dimer (Wajcman 2005). Variants in this region commonly lead to high oxygen affinity and reduced cooperativity (Wajcman 2005), which has been observed for the Hb Tarrant variant (Moo-Penn 1977). This variant is found on a single chromosome in the Genome Aggregation Database (1/248750 alleles), indicating it is not a common polymorphism. Based on available information, this variant is considered to be pathogenic dominant for mild erythrocytosis. References: Link to variant in HbVar database: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=188 Ibarra B et al. Heterozygosity and homozygosity for the high oxygen affinity hemoglobin Tarrant or alpha 126 (H9) Asp replaced by Asn in two Mexican families. Hemoglobin. 1981;5(4):337-48. Ip KL et al. Hb Tarrant (a126(H9)Asp?Asn; HBA2: c.379G?>?A (or HBA1)) in a Chinese Family as a Cause of Familial Erythrocytosis. Hemoglobin. 2016 Aug;40(4):260-3. Moo-Penn WF et al. Hemoglobin Tarrant: alpha126(H9) Asp leads to Asn. A new hemoglobin variant in the alpha1beta1 contact region showing high oxygen affinity and reduced cooperativity. Biochim Biophys Acta. 1977 Feb 22;490(2):443-51. Wajcman H et al. Hemoglobins with high oxygen affinity leading to erythrocytosis. New variants and new concepts. Hemoglobin. 2005;29(2):91-106.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284150 SCV001469776 pathogenic not provided 2020-09-09 criteria provided, single submitter clinical testing The best available variant frequency is uninformative because there are too few occurrences in population data. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function.
OMIM RCV000016948 SCV000037220 other HEMOGLOBIN TARRANT 2013-03-28 no assertion criteria provided literature only

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