ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1994C>T (p.Ser665Phe)

gnomAD frequency: 0.00188  dbSNP: rs145891889
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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129662 SCV000184460 likely benign Hereditary cancer-predisposing syndrome 2015-09-09 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification;Subpopulation frequency in support of benign classification
Invitae RCV000200171 SCV000252676 benign Neurofibromatosis, type 1 2020-12-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000121628 SCV000269447 benign not specified 2015-04-07 criteria provided, single submitter clinical testing p.Ser665Phe in exon 17 of NF1: This variant is not expected to have clinical sig nificance because it has been identified in 0.8% (81/10324) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs145891889).
GeneDx RCV000587577 SCV000521058 benign not provided 2021-05-05 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 10712197, 24803665, 15060124, 24728327, 27322474, 23771920, 28371134, 26154128, 33562071)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000121628 SCV000696388 benign not specified 2019-01-30 criteria provided, single submitter clinical testing Variant summary: NF1 c.1994C>T (p.Ser665Phe) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00074 in 282364 control chromosomes, predominantly within the African subpopulation at a frequency of 0.0077 in the gnomAD database, including 2 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 37-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. However, this region is affected by pseudogene interference therefore these population frequency data need to be cautiously considered. c.1994C>T has been reported in the literature in an affected individual (Fahsold 2000). This report however does not provide unequivocal conclusions about association of the variant with Neurofibromatosis Type 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant predominantly as likely benign/benign (7x) and once as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000200171 SCV000781933 likely benign Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000200171 SCV000803613 uncertain significance Neurofibromatosis, type 1 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Uncertain Significance - Insufficient Evidence, for Neurofibromatosis 1, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder.
PreventionGenetics,PreventionGenetics RCV000121628 SCV000806260 benign not specified 2016-05-11 criteria provided, single submitter clinical testing
Mendelics RCV000200171 SCV000839134 likely benign Neurofibromatosis, type 1 2018-07-02 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001124835 SCV001283831 benign Neurofibromatosis, familial spinal 2017-11-20 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services,Illumina RCV001124836 SCV001283832 benign Neurofibromatosis-Noonan syndrome 2017-11-20 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services,Illumina RCV001124837 SCV001283833 benign Café-au-lait macules with pulmonary stenosis 2017-11-20 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services,Illumina RCV000200171 SCV001283834 benign Neurofibromatosis, type 1 2017-11-20 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Genome Diagnostics Laboratory,The Hospital for Sick Children RCV000200171 SCV001479096 likely benign Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000121628 SCV002066473 likely benign not specified 2020-02-03 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000129662 SCV002527436 benign Hereditary cancer-predisposing syndrome 2020-07-31 criteria provided, single submitter curation
Medical Genetics, University of Parma RCV000200171 SCV002567760 benign Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
ITMI RCV000121628 SCV000085826 not provided not specified 2013-09-19 no assertion provided reference population

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