ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4010G>A (p.Arg1337Gln)

dbSNP: rs1060500379
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000456397 SCV000542222 benign Neurofibromatosis, type 1 2025-02-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002318999 SCV001183299 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-12-15 criteria provided, single submitter clinical testing The p.R1337Q variant (also known as c.4010G>A), located in coding exon 30 of the NF1 gene, results from a G to A substitution at nucleotide position 4010. The arginine at codon 1337 is replaced by glutamine, an amino acid with highly similar properties. This alteration was observed in 0/7,051 unselected female breast cancer patients and was observed with an allele frequency of 0.00009 in 11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV002056708 SCV002496266 uncertain significance not provided 2023-03-24 criteria provided, single submitter clinical testing Has not been observed in patients with NF1-related features to our knowledge, but has been reported in a control group (Momozawa et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29106415, 30287823, 25486365, 22807134)
Genome-Nilou Lab RCV000456397 SCV002560362 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002481368 SCV002778548 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2022-05-04 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004737494 SCV005342610 uncertain significance NF1-related disorder 2024-03-27 no assertion criteria provided clinical testing The NF1 c.4010G>A variant is predicted to result in the amino acid substitution p.Arg1337Gln. To our knowledge, this variant has not been reported in individuals with NF1 related disorders in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/404606/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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