Submissions for variant NM_000518.5(HBB):c.110del (p.Pro37fs)

dbSNP: rs267607297

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586096	SCV000697057	pathogenic	beta Thalassemia	2024-03-05	criteria provided, single submitter	clinical testing	Variant summary: HBB c.110delC (p.Pro37LeufsX25) 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. The variant was absent in 251358 control chromosomes. c.110delC has been reported in the literature in multiple individuals affected with Beta Thalassemia (example, Yang_1989, Shaji_2003, Rujito_2015). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 15424). Based on the evidence outlined above, the variant was classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759790	SCV000889359	pathogenic	not provided	2023-11-02	criteria provided, single submitter	clinical testing	The HBB c.110del (p.Pro37Leufs*25) variant alters the translational reading frame of the HBB mRNA and causes the premature termination of HBB protein synthesis. This variant has been reported in the published literature to be associated with beta(0)-thalassemia, including many individuals affected with beta-thalassemia or in heterozygous carriers showing hematological evidence of thalassemia trait, especially in southeast Asian populations (see HbVar (http://globin.cse.psu.edu/cgi-bin/hbvar/counter), PMID: 2736244 (1989), 12709369 (2003), 21077770 (2010), 22335963 (2012), 23682686 (2013), 26291967 (2015), 31890591 (2019), 32638316 (2020)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.
Revvity Omics, Revvity	RCV000759790	SCV002023454	likely pathogenic	not provided	2021-04-10	criteria provided, single submitter	clinical testing
OMIM	RCV000016680	SCV000036950	pathogenic	Beta zero thalassemia	1989-05-01	no assertion criteria provided	literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	RCV000586096	SCV001244469	pathogenic	beta Thalassemia	2019-11-25	no assertion criteria provided	curation
Natera, Inc.	RCV000586096	SCV001453783	pathogenic	beta Thalassemia	2020-09-16	no assertion criteria provided	clinical testing