ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4444A>C (p.Asn1482His) (rs1555618837)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570225 SCV000663238 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000681287 SCV000808749 uncertain significance not provided 2018-05-10 criteria provided, single submitter clinical testing This variant is denoted NF1 c.4444A>C at the cDNA level, p.Asn1482His (N1482H) at the protein level, and results in the change of an Asparagine to a Histidine (AAT>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Asn1482His was not observed in large population cohorts (Lek 2016). This variant is located within the GTPase activating protein domain (Thomas 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether NF1 Asn1482His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000707229 SCV000836317 uncertain significance Neurofibromatosis, type 1 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 1482 of the NF1 protein (p.Asn1482His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 480196). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; 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.

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