Submissions for variant NM_000492.4(CFTR):c.3371_3373del (p.Glu1124del)

dbSNP: rs397508548

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001804780	SCV002051081	uncertain significance	not specified	2021-12-13	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.3371_3373delAAG (p.Glu1124del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant allele was found at a frequency of 8e-06 in 250910 control chromosomes (gnomAD). c.3371_3373delAAG has been reported in the literature in a homozygous individual affected with congenital bilateral absence of the vas deferens and chronic pancreatitis (Conway_2002). Furthermore, the variant was detected along with F508del in a compound heterozygous patient affected with idiopathic chronic pancreatitis (Masson_2013). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Ambry Genetics	RCV000577000	SCV002616814	uncertain significance	Cystic fibrosis	2021-01-13	criteria provided, single submitter	clinical testing	The c.3371_3373delAAG variant (also known as p.E1124del) is located in coding exon 21 of the CFTR gene. This variant results from an in-frame AAG deletion at nucleotide positions 3371 to 3373. This results in the in-frame deletion of a glutamic acid at codon 1124. This variant was first reported in a homozygous Pakistani male with congenital absence of the vas deferens, pancreatitis, and normal sweat chloride levels (Conway SP et al. Pediatr. Pulmonol., 2002 Dec;34:491-5). It was also identified in the homozygous state in another Pakistani individual with cystic fibrosis, elevated immunoreactive trypsinogen, and a borderline sweat chloride level (Lim MT et al. Arch. Dis. Child., 2014 Mar;99:197-202). In an individual with idiopathic chronic pancreatitis, this variant was identified with CFTR p.F508del and SPINK1 p.N34S (Masson E et al. PLoS One, 2013 Aug;8:e73522). In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002483056	SCV002779629	uncertain significance	Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation	2022-04-20	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577000	SCV000679064	not provided	Cystic fibrosis		no assertion provided	literature only