Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001246537 | SCV001419896 | uncertain significance | Cystic fibrosis | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 988 of the CFTR protein (p.Pro988Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Johns Hopkins Genomics, |
RCV001246537 | SCV002570372 | uncertain significance | Cystic fibrosis | 2022-07-23 | criteria provided, single submitter | clinical testing | This CFTR variant (rs1792306616) is absent from a large population dataset and has not been reported in the literature, to our knowledge. This variant has been reported in ClinVar. Three bioinformatic tools queried predict that this substitution would be damaging and the proline residue at this position is evolutionarily conserved across all species assessed. We consider the clinical significance of CFTR c.2963C>T to be uncertain at this time. |
Ambry Genetics | RCV001246537 | SCV002752060 | uncertain significance | Cystic fibrosis | 2021-10-19 | criteria provided, single submitter | clinical testing | The p.P988L variant (also known as c.2963C>T), located in coding exon 18 of the CFTR gene, results from a C to T substitution at nucleotide position 2963. The proline at codon 988 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001835271 | SCV002083568 | uncertain significance | CFTR-related disorders | 2019-01-15 | no assertion criteria provided | clinical testing |