ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.7468G>C (p.Val2490Leu) (rs2230850)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130554 SCV000185424 likely benign Hereditary cancer-predisposing syndrome 2015-07-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,In silico models in agreement (benign)
GeneDx RCV000680358 SCV000529106 likely benign not provided 2018-01-22 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.
Genetic Services Laboratory, University of Chicago RCV000121639 SCV000595976 likely benign not specified 2016-07-26 criteria provided, single submitter clinical testing
ITMI RCV000121639 SCV000085837 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000121639 SCV000919885 benign not specified 2018-08-13 criteria provided, single submitter clinical testing Variant summary: NF1 c.7468G>C (p.Val2490Leu) results in a conservative amino acid change in the encoded protein sequence that is located outside of any known functional domains. Four of five in-silico tools predict a benign effect of the variant on protein function. The observed variant frequency within African control individuals in the gnomAD database is approximately 25 fold of the estimated maximal expected allele frequency for a pathogenic variant in NF1 causing Neurofibromatosis Type 1 phenotype (0.00021), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.7468G>C in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (1x) or likely benign (4x). Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000199322 SCV000252690 benign Neurofibromatosis, type 1 2018-01-05 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000121639 SCV000270628 likely benign not specified 2016-03-15 criteria provided, single submitter clinical testing p.Val2511Leu in exon 51 of NF1: This variant is not expected to have clinical si gnificance because it has been identified in 0.6% (58/10402) of African chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/; dbSNP rs2230850).

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