ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4144G>A (p.Gly1382Ser) (rs138227618)

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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 RCV000130328 SCV000185178 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-14 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000197840 SCV000254501 uncertain significance Neurofibromatosis, type 1 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 1382 of the NF1 protein (p.Gly1382Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs138227618, ExAC 0.009%). This variant has been observed in individuals with breast cancer, as well as unaffected controls (PMID: 30287823). This variant is also known as c.4207G>A (p.Gly1403Ser) in the literature. ClinVar contains an entry for this variant (Variation ID: 141711). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000680999 SCV000808448 uncertain significance not provided 2018-02-19 criteria provided, single submitter clinical testing This variant is denoted NF1 c.4144G>A at the cDNA level, p.Gly1382Ser (G1382S) at the protein level, and results in the change of a Glycine to a Serine (GGT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Gly1382Ser was observed at an allele frequency of 0.009% (11/126504) in individuals of European (Non-Finnish) ancestry in large population cohorts (Lek 2016). This variant is located within the GTPase activating protein domain (Thomas 2012, Luo 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether NF1 Gly1382Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV001126022 SCV001285166 uncertain significance Neurofibromatosis-Noonan syndrome 2017-04-27 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001126023 SCV001285167 uncertain significance Café-au-lait macules with pulmonary stenosis 2017-04-27 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000197840 SCV001285168 uncertain significance Neurofibromatosis, type 1 2017-04-27 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001126024 SCV001285169 uncertain significance Neurofibromatosis, familial spinal 2017-04-27 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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