Submissions for variant NM_001211.6(BUB1B):c.1168GAG[1] (p.Glu391del)

dbSNP: rs778590557

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002230306	SCV000541091	uncertain significance	Mosaic variegated aneuploidy syndrome 1	2024-12-18	criteria provided, single submitter	clinical testing	This variant, c.1171_1173del, results in the deletion of 1 amino acid(s) of the BUB1B protein (p.Glu391del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs778590557, gnomAD 0.06%). This variant has been observed in individual(s) with colorectal cancer (PMID: 27239782). This variant is also known as p.Glu390del. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV002230306	SCV001737434	uncertain significance	Mosaic variegated aneuploidy syndrome 1	2023-11-13	criteria provided, single submitter	clinical testing	The BUB1B c.1171_1173del (p.Glu391del) change has a maximum subpopulation frequency of 0.065% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The change results in the deletion of a single glutamic acid residue in the BUB3-binding domain. Functional studies indicate that this variant does not affect binding to the spindle assembly checkpoint proteins BUB1 and BUB3 (PMID: 27239782). This variant has been reported in an individual with colorectal cancer (PMID: 27239782). This variant is also known as p.Glu390del in the literature. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV002469151	SCV002010632	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
GeneDx	RCV002469151	SCV002765470	uncertain significance	not provided	2022-06-13	criteria provided, single submitter	clinical testing	In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV002481362	SCV002790800	uncertain significance	Mosaic variegated aneuploidy syndrome 1; Premature chromatid separation trait; Colorectal cancer	2022-02-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002522756	SCV003693033	uncertain significance	Inborn genetic diseases	2024-12-04	criteria provided, single submitter	clinical testing	The c.1171_1173delGAG (p.E391del) alteration is located in exon 9 (coding exon 9) of the BUB1B gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.1171 and c.1173, resulting in the deletion of 1 residue. This variant was detected in two siblings who had early-onset colorectal cancer and breast cancer (<50y); however, it was also detected in their unaffected brother, and in healthy control individuals (Hahn, 2016). Experimental studies showed no significant difference in the binding of BUB1 or BUB3 to BUBR1 between this alteration and wild type (Hahn, 2016). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.