ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4055G>C (p.Ser1352Thr)

gnomAD frequency: 0.00001  dbSNP: rs876660908
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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 RCV000220527 SCV000278712 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-24 criteria provided, single submitter clinical testing The p.S1352T variant (also known as c.4055G>C), located in coding exon 30 of the NF1 gene, results from a G to C substitution at nucleotide position 4055. The serine at codon 1352 is replaced by threonine, an amino acid with 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. 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 through the opossum, but is not conserved in lower 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 p.S1352T remains unclear.
Invitae RCV000531590 SCV000628564 likely benign Neurofibromatosis, type 1 2023-12-25 criteria provided, single submitter clinical testing
GeneDx RCV001589161 SCV001824517 uncertain significance not provided 2023-05-26 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 pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22807134, 25486365, 28873162, 36200007)
Genome-Nilou Lab RCV000531590 SCV002560370 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002494600 SCV002789634 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2022-03-19 criteria provided, single submitter clinical testing
Baylor Genetics RCV003463603 SCV004198372 uncertain significance Juvenile myelomonocytic leukemia 2023-08-11 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004547563 SCV004717066 uncertain significance NF1-related disorder 2023-12-12 criteria provided, single submitter clinical testing The NF1 c.4055G>C variant is predicted to result in the amino acid substitution p.Ser1352Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-29576082-G-C). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/234185/). 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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