ClinVar Miner

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

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Total submissions: 5
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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 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
Invitae RCV000205363 SCV000261449 uncertain significance Neurofibromatosis, type 1 2019-12-11 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 observed 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.
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.
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
GenomeConnect, ClinGen RCV000205363 SCV001423441 not provided Neurofibromatosis, type 1 no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 04-29-2017 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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