Submissions for variant NM_000492.4(CFTR):c.1820_1903del (p.Met607_Gln634del)

dbSNP: rs121908777

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046486	SCV001981571	pathogenic	Cystic fibrosis	2021-09-24	reviewed by expert panel	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000046486	SCV000696875	pathogenic	Cystic fibrosis	2025-03-03	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.1820_1903del84 (p.Met607_Gln634del) results in an in-frame deletion that is predicted to remove 28 amino acids from the encoded protein. The variant allele was found at a frequency of 9.3e-06 in 966448 control chromosomes. c.1820_1903del84 has been reported in the literature in multiple individuals affected with Cystic Fibrosis. 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. The following publications have been ascertained in the context of this evaluation (PMID: 15371903, 1373934, 17331079, 10777364, 21520337, 21474639, 1284539). ClinVar contains an entry for this variant (Variation ID: 53396). Based on the evidence outlined above, the variant was classified as pathogenic.
CFTR-France	RCV000046486	SCV001169426	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000046486	SCV001193958	likely pathogenic	Cystic fibrosis	2019-12-04	criteria provided, single submitter	clinical testing	NM_000492.3(CFTR):c.1820_1903del84(aka M607_Q643del) is classified as likely pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 1373934, 15371903, 10875853, 15858154, 21520337, 10777364, 21474639 and 1284539. Classification of NM_000492.3(CFTR):c.1820_1903del84(aka M607_Q643del) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Johns Hopkins Genomics, Johns Hopkins University	RCV000046486	SCV001469038	likely pathogenic	Cystic fibrosis	2020-12-07	criteria provided, single submitter	clinical testing	This CFTR variant is predicted to result in an in-frame deletion of 28 amino acids. It has been identified in multiple individuals with a classic cystic fibrosis phenotype. This variant has been reported in ClinVar. We consider c.1820_1903del to be likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000046486	SCV002240170	pathogenic	Cystic fibrosis	2023-12-28	criteria provided, single submitter	clinical testing	This variant, c.1820_1903del, results in the deletion of 28 amino acid(s) of the CFTR protein (p.Met607_Gln634del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 1373934, 21520337). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 53396). This variant disrupts the p.Asp614 amino acid residue in CFTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9736778, 12454843, 17413420, 21679131). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV004558294	SCV005046899	pathogenic	not provided	2022-09-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005042130	SCV005673340	pathogenic	Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation	2024-02-28	criteria provided, single submitter	clinical testing
3billion	RCV000046486	SCV005905606	pathogenic	Cystic fibrosis	2023-08-11	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Inframe deletion located in a nonrepeat region - predicted to change the length of the protein and disrupt normal protein function. The variant has been reported multiple times as an established pathogenic variant (ClinVar ID: VCV000053396 / PMID: 1373934). Therefore, the variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
OMIM	RCV000046486	SCV000027769	pathogenic	Cystic fibrosis	1992-05-01	no assertion criteria provided	literature only