ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.7441G>C (p.Gly2481Arg) (rs1555536357)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562336 SCV000666683 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (benign),Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae RCV000803731 SCV000943615 uncertain significance Neurofibromatosis, type 1 2018-11-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 2481 of the NF1 protein (p.Gly2481Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. 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: 481894). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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