Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000664921 | SCV000788954 | likely pathogenic | Cystic fibrosis | 2016-12-22 | criteria provided, single submitter | clinical testing | |
CFTR- |
RCV000664921 | SCV001169508 | pathogenic | Cystic fibrosis | 2018-01-29 | criteria provided, single submitter | curation | |
Neuberg Centre For Genomic Medicine, |
RCV000664921 | SCV002073087 | pathogenic | Cystic fibrosis | criteria provided, single submitter | clinical testing | The splice acceptor variant c.274-1G>C in CFTR (NM_000492.4) has been previously reported in an affected patient (Claustres M et al). The variant has been submitted to ClinVar as Pathogenic. The c.274-1G>C variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant affects an invariant splice nucleotide and hence is predicted to cause loss of function. For these reasons, this variant has been classified as Pathogenic. | |
Labcorp Genetics |
RCV000664921 | SCV002245860 | pathogenic | Cystic fibrosis | 2023-02-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 53554). This variant is also known as 406-1G>C. Disruption of this splice site has been observed in individual(s) with cystic fibrosis (PMID: 1284541, 15365999). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 3 of the CFTR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000664921 | SCV002600702 | likely pathogenic | Cystic fibrosis | 2022-10-24 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.274-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 3' acceptor site. Three predict the variant creates a cryptic 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250598 control chromosomes. c.274-1G>C has been reported in the literature in at leat one individual affected with Cystic Fibrosis (Bonizzato_1992, Lucarelli_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Baylor Genetics | RCV004566874 | SCV005057479 | pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2023-11-13 | criteria provided, single submitter | clinical testing |