ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.958T>G (p.Leu320Val) (rs144476686)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000029549 SCV000075309 uncertain significance Cystic fibrosis 2017-09-16 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 320 of the CFTR protein (p.Leu320Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs144476686, ExAC 0.2%). This variant has been reported in individuals undergoing testing for cystic fibrosis (PMID: 15858154, 20706124) and chronic pancreatitis (PMID: 23951356, 20460946, 17003641), as well as in an individual with Bohring–Opitz syndrome (PMID: 26364555). ClinVar contains an entry for this variant (Variation ID: 35894). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000590210 SCV000697062 uncertain significance not provided 2016-09-29 criteria provided, single submitter clinical testing Variant summary: c.958T>G affects a non-conserved nucleotide, resulting in amino acid change from Leu to Val. 3/5 in-silico tools predict this variant to be benign. This variant was found in 50/121238 control chromosomes at a frequency of 0.0004124, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0129603). This mutation has been reported in association with various CF-related phenotypes or phenotypes in the CF spectrum (n=2; Lucarelli and Shrijver publications), CBAVD (n=1; sickkids), chronic pancreatitis (n=3; Pelletier, Keiles and Schwartz publications), and bronchiectasis (mentioned in Pelletier publication; exact number not known). The variant was also reported in newborns from newborn screening, and when not part of a complex allele and when in combination with a CF-C mutation, patients with this variant had normal sweat chloride levels and no cases of pancreatic insufficiency, which the authors suggest indicate the variant to be non-CF causing (Salinas_2016). Of note, this variant has been observed in three internal subjects undergoing testing for CF who also carry deltaF508 but phase and clinical information is not known. In HGMD, the variant has been listed to be associated with the CBAVD phenotype. In the sickkids db, this variant was reported to be observed in a CBAVD pt who was compound heterozygous for this variant and deltaF508. Taken all together, this variant was classified as VUS. More concordant occurrences and controls data are needed to establish a clear association to a specific phenotype.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000590210 SCV000855679 uncertain significance not provided 2018-06-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590210 SCV000889319 uncertain significance not provided 2017-12-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000029549 SCV000052201 uncertain significance Cystic fibrosis 2015-10-02 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.