ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.769C>A (p.Pro257Thr)

gnomAD frequency: 0.00008  dbSNP: rs387906776
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
Eurofins Ntd Llc (ga) RCV000294434 SCV000336020 uncertain significance not provided 2015-10-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001061626 SCV001226374 uncertain significance Atrial septal defect 7 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 257 of the NKX2-5 protein (p.Pro257Thr). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. ClinVar contains an entry for this variant (Variation ID: 283727). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002503988 SCV002817048 uncertain significance Atrial septal defect 7; Conotruncal heart malformations; Hypothyroidism, congenital, nongoitrous, 5; Tetralogy of Fallot; Ventricular septal defect 3; Hypoplastic left heart syndrome 2 2021-10-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV003165731 SCV003858934 uncertain significance Cardiovascular phenotype 2022-12-09 criteria provided, single submitter clinical testing The p.P257T variant (also known as c.769C>A), located in coding exon 2 of the NKX2-5 gene, results from a C to A substitution at nucleotide position 769. The proline at codon 257 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000294434 SCV005370655 uncertain significance not provided 2023-06-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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.