Submissions for variant NM_000518.5(HBB):c.114_120del (p.Pro37_Trp38insTer)

dbSNP: rs63750099

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003114196	SCV003799764	pathogenic	not provided	2022-11-29	criteria provided, single submitter	clinical testing	The HBB c.114_120del; p.Trp38Ter variant (also known as Trp37Ter when numbered from the mature protein, rs63750099, HbVar ID: 842) is reported in the literature in individuals affected with beta(0)-thalassemia (Schnee 1989, Vetter 1997). This variant is also reported in ClinVar (Variation ID: 15427) but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Schnee J et al. Beta-thalassemia gene analysis in a Turkish family reveals a 7 BP deletion in the coding region. Blood. 1989 Jun;73(8):2224-5. PMID: 2730955. Vetter B et al. Beta-thalassaemia in the immigrant and non-immigrant German populations. Br J Haematol. 1997 May;97(2):266-72. PMID: 9163586.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001078349	SCV003844975	pathogenic	beta Thalassemia	2023-02-19	criteria provided, single submitter	clinical testing	Variant summary: HBB c.114_120delGACCCAG (p.Trp38X), also known as 37-39 (-7 bp), results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251392 control chromosomes (gnomAD). c.114_120delGACCCAG has been reported in the literature as a biallelic genotype in individuals affected with Beta Thalassemia (e.g. Schnee_1989, Vetter_1997). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM	RCV000016684	SCV000036954	pathogenic	Beta zero thalassemia	1989-06-01	no assertion criteria provided	literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	RCV001078349	SCV001244537	pathogenic	beta Thalassemia	2019-11-25	no assertion criteria provided	curation