Submissions for variant NM_000518.5(HBB):c.380_396del (p.Val127fs)

dbSNP: rs750606223

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001982926	SCV002238492	pathogenic	not provided	2021-01-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with autosomal recessive beta-thalassemia (PMID: 8535446, 31190580). This variant is also known as Hb Westdale. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Val127Glufs*8) in the HBB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acid(s) of the HBB protein.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004699591	SCV005205050	pathogenic	beta Thalassemia	2024-06-07	criteria provided, single submitter	clinical testing	Variant summary: HBB c.380_396del17 (p.Val127GlufsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein. The variant allele was found at a frequency of 4e-06 in 251350 control chromosomes. c.380_396del17 has been reported in the literature in multiple individuals affected with autosomal recessive beta-thalassemia (examples: Waye_1995, Dehury_2019, Tripathi_2020). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 31190580, 32296912, 8535446). ClinVar contains an entry for this variant (Variation ID: 1459872). Based on the evidence outlined above, the variant was classified as pathogenic.