Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001068414 | SCV001233526 | uncertain significance | Cystic fibrosis | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 1287 of the CFTR protein (p.Gly1287Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230633 | SCV003929015 | uncertain significance | not specified | 2023-04-27 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.3859G>A (p.Gly1287Arg) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250722 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3859G>A in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV001068414 | SCV001454287 | uncertain significance | Cystic fibrosis | 2020-09-16 | no assertion criteria provided | clinical testing |