ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.575G>A (p.Arg192Gln)

gnomAD frequency: 0.00001  dbSNP: rs587781670
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129826 SCV000184641 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-08 criteria provided, single submitter clinical testing The p.R192Q variant (also known as c.575G>A), located in coding exon 5 of the NF1 gene, results from a G to A substitution at nucleotide position 575. The arginine at codon 192 is replaced by glutamine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project.To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 110000 alleles tested) in our clinical cohort. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.R192Q remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000476088 SCV000542153 likely benign Neurofibromatosis, type 1 2024-01-21 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765343 SCV000896607 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2018-10-31 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000476088 SCV001479269 uncertain significance Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
GeneDx RCV001549489 SCV001769646 likely benign not provided 2020-09-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast cancer (Penkert 2018); Observed with a truncating NF1 variant, phase (cis or trans) unknown, in an individual with neurofibromatosis type 1 (Wu-Chou 2018); This variant is associated with the following publications: (PMID: 30086788, 30287823, 30290804)
Ambry Genetics RCV002345443 SCV002651283 benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-09-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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