ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.4200_4201del (p.Cys1400_Glu1401delinsTer)

dbSNP: rs397508695
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR-France RCV001009423 SCV001169372 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Ambry Genetics RCV001009423 SCV002630659 pathogenic Cystic fibrosis 2018-09-25 criteria provided, single submitter clinical testing The c.4200_4201delTG pathogenic mutation, located in coding exon 26 of the CFTR gene, results from a deletion of two nucleotides at nucleotide positions 4200 to 4201. This changes the amino acid from a cysteine to a stop codon within coding exon 26 (p.C1400*). This mutation was identified in two males with congenital absence of the vas deference (CBAVD) in conjunction with p.R117H (Steiner B et al. Hum. Mutat., 2011 Aug;32:912-20). BHK-21 cells expressing p.C1400* demonstrated reduced mature protein levels, with none at the cell surface, and reduced chloride channel activity compared to wild type (Gentzsch M et al. J. Biol. Chem., 2001 Jan;276:1291-8). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV001009423 SCV003440219 pathogenic Cystic fibrosis 2022-04-28 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individual(s) with clinical features of CFTR-associated conditions (PMID: 2152033, 21520337, 28603918). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys1400*) in the CFTR gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 81 amino acid(s) of the CFTR protein. ClinVar contains an entry for this variant (Variation ID: 53917). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CFTR protein in which other variant(s) (p.Gln1476*) have been determined to be pathogenic (PMID: 11938439, 22020151, 25910067, 28544683). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing.
Fulgent Genetics, Fulgent Genetics RCV005042147 SCV005666440 pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation 2024-03-11 criteria provided, single submitter clinical testing

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