Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001203316 | SCV001374473 | uncertain significance | Cystic fibrosis | 2022-07-12 | criteria provided, single submitter | clinical testing | 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 C0"). 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. ClinVar contains an entry for this variant (Variation ID: 934842). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 444 of the CFTR protein (p.Ile444Met). |
| Ambry Genetics | RCV001203316 | SCV002693090 | uncertain significance | Cystic fibrosis | 2020-10-13 | criteria provided, single submitter | clinical testing | The p.I444M variant (also known as c.1332T>G), located in coding exon 10 of the CFTR gene, results from a T to G substitution at nucleotide position 1332. The isoleucine at codon 444 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |