ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1620G>T (p.Glu540Asp) (rs766748586)

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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 RCV000166167 SCV000216942 uncertain significance Hereditary cancer-predisposing syndrome 2015-11-18 criteria provided, single submitter clinical testing In silico models in agreement (benign);Rarity in general population databases (dbsnp, esp, 1000 genomes);Insufficient or conflicting evidence
Invitae RCV000553024 SCV000628377 uncertain significance Neurofibromatosis, type 1 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 540 of the NF1 protein (p.Glu540Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs766748586, ExAC 0.03%) but has not been reported in the literature in individuals with a NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 186553). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. 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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