ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1588G>A (p.Val530Ile) (rs145191978)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129860 SCV000184677 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761180 SCV000891096 uncertain significance Acute monocytic leukemia; Acute monoblastic leukemia 2017-04-21 no assertion criteria provided clinical testing
GeneDx RCV000489208 SCV000577596 likely benign not provided 2018-01-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000205363 SCV000261449 uncertain significance Neurofibromatosis, type 1 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 530 of the NF1 protein (p.Val530Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs145191978, ExAC 0.009%). This variant has been reported in an individual affected with pheochromocytoma, who also carried a pathogenic SDHB variant (PMID: 23407919). ClinVar contains an entry for this variant (Variation ID: 141369). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. 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.

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.