Total submissions: 11
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Prevention |
RCV000242518 | SCV000304477 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
| Eurofins Ntd Llc |
RCV000725286 | SCV000335702 | uncertain significance | not provided | 2018-02-06 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000725286 | SCV000602986 | benign | not provided | 2022-03-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001087241 | SCV000751426 | likely benign | Cystic fibrosis | 2024-01-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000242518 | SCV000919151 | benign | not specified | 2018-02-21 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.1920T>C alters a non-conserved nucleotide resulting in a synonymous change (p.Phe640=). 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.7e-05 in 276596 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (4.7e-05 vs 0.013), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1920T>C in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported via publications. The variant was reported in the databases to be present on the same allele as a complex pathogenic allele (c.220C>T_c.601G>A_c.3808G>A). In addition, our laboratory has identified the variant in numerous (>20) individuals with the same pathogenic complex allele, and in several of these cases a second pathogenic CFTR variant was also identified (e.g. p.Phe508del (in 2 cases), p.Ile507del (in one case), p.Arg1162X (in one case), c.5T_TG12 (in one case)). These co-occurrences with other pathogenic variants provide supporting evidence for a benign role. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, where one laboratory classified the variant as benign, and the other laboratory as uncertain significance. Based on the evidence outlined above, the variant was classified as benign. |
| Ambry Genetics | RCV001087241 | SCV001174323 | likely benign | Cystic fibrosis | 2014-11-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Johns Hopkins Genomics, |
RCV001087241 | SCV001430644 | likely benign | Cystic fibrosis | 2020-06-11 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV001087241 | SCV001822092 | likely benign | Cystic fibrosis | 2021-07-22 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV001589232 | SCV001822093 | uncertain significance | Congenital bilateral aplasia of vas deferens from CFTR mutation | 2021-07-22 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000725286 | SCV002047275 | likely benign | not provided | 2021-01-12 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001835741 | SCV002080686 | likely benign | CFTR-related disorder | 2018-04-05 | no assertion criteria provided | clinical testing |