ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3749G>A (p.Arg1250Gln)

gnomAD frequency: 0.00001  dbSNP: rs199474765
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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 RCV000222757 SCV000277688 uncertain significance Hereditary cancer-predisposing syndrome 2015-08-10 criteria provided, single submitter clinical testing The p.R1250Q variant (also known as c.3749G>A), located in coding exon 28 of the NF1 gene, results from a G to A substitution at nucleotide position 3749. The arginine at codon 1250 is replaced by glutamine, an amino acid with highly similar properties. This alteration wasdetected in acohortof 30non-aneuploidfetuses and neonateswith diverse structural abnormalities first identified by prenatal ultrasound (CarssKJ et al.Hum Mol Genet. 2014 Jun 15;23(12):3269-77).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. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 55000alleles tested) in our clinical cohort.This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of p.R1250Qremains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000806752 SCV000946768 likely benign Neurofibromatosis, type 1 2025-01-05 criteria provided, single submitter clinical testing
GeneDx RCV001778813 SCV002015375 uncertain significance not provided 2021-05-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as a germline pathogenic or benign variant in individual(s) with neurofibromatosis type 1 to our knowledge; This variant is associated with the following publications: (PMID: 24476948, 33935721, 25486365, 22807134, 32697994)
Genome-Nilou Lab RCV000806752 SCV002560326 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV003462522 SCV004198226 uncertain significance Juvenile myelomonocytic leukemia 2024-02-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV004558566 SCV005047733 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-12-09 criteria provided, single submitter clinical testing The c.3749G>A (p.R1250Q) alteration is located in exon 28 (coding exon 28) of the NF1 gene. This alteration results from a G to A substitution at nucleotide position 3749, causing the arginine (R) at amino acid position 1250 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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