Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
RCV001200887 | SCV001371797 | uncertain significance | Cystic fibrosis | 2020-01-07 | criteria provided, single submitter | clinical testing | CFTR c.4037>A has not been reported in the literature in patients with cystic fibrosis to our knowledge. It is absent from ClinVar. This CFTR variant (rs1313341594) is rare (<0.1%) in a large population dataset (gnomAD: 2/282570 total alleles; 0.0007%; no homozygotes). Three bioinformatic tools queried predict that this substitution would be probably be damaging and the leucine residue at this position is evolutionarily conserved in all species assessed. Due to insufficient evidence that this variant is deleterious, we consider the clinical significance of c.4037T>A to be uncertain at this time. |
Ambry Genetics | RCV001200887 | SCV002625242 | uncertain significance | Cystic fibrosis | 2015-08-12 | criteria provided, single submitter | clinical testing | The p.L1346Q variant (also known as c.4037T>A), located in coding exon 25 of the CFTR gene, results from a T to A substitution at nucleotide position 4037. The leucine at codon 1346 is replaced by glutamine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. 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 variant remains unclear. |
Invitae | RCV001200887 | SCV002988305 | uncertain significance | Cystic fibrosis | 2022-08-23 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 932918). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 1346 of the CFTR protein (p.Leu1346Gln). |