Submissions for variant NM_001081.4(CUBN):c.6894_6901dup (p.Leu2301Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002471966	SCV002767656	pathogenic	Imerslund-Grasbeck syndrome type 1	2020-05-21	criteria provided, single submitter	clinical testing	A heterozygous duplication variant was identified, NM_001081.3(CUBN):c.6894_6901dup in exon 45 of 67 of the CUBN gene. This duplication variant is predicted to result in a change of a leucine to a stop at amino acid position 2301 of the protein; NP_001072.2(CUBN):p.(Leu2301*), resulting in the loss of normal protein function through nonsense-mediated decay (NMD). The variant is present in the gnomAD population database at a frequency of 0.003% (1 heterozygote; 0 homozygotes). The variant has not been previously reported in clinical cases, however, other variants predicted to cause NMD have been reported as pathogenic in individuals with CUBN-related nephropathy (ClinVar). Subsequent analysis of parental samples indicated that this variant was paternally inherited. Based on information available at the time of curation, this variant has been classified as PATHOGENIC.
Fulgent Genetics, Fulgent Genetics	RCV005032284	SCV005672709	likely pathogenic	Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign	2024-02-20	criteria provided, single submitter	clinical testing