ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.889G>T (p.Val297Phe)

dbSNP: rs569535312
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000532333 SCV000644785 uncertain significance Atrial septal defect 7 2017-05-13 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 297 of the NKX2-5 protein (p.Val297Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs569535312, ExAC 0.02%) but has not been reported in the literature in individuals with a NKX2-5-related disease.
Ambry Genetics RCV000617437 SCV000737120 uncertain significance Cardiovascular phenotype 2016-09-10 criteria provided, single submitter clinical testing The p.V297F variant (also known as c.889G>T), located in coding exon 2 of the NKX2-5 gene, results from a G to T substitution at nucleotide position 889. The valine at codon 297 is replaced by phenylalanine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs569535312. Based on data from ExAC, the T allele has an overall frequency less than 0.01% (1/104724). 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 alteration remains unclear.

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.