ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.278G>A (p.Cys93Tyr) (rs199474728)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000466535 SCV000925777 likely pathogenic Neurofibromatosis, type 1 2018-09-27 no assertion criteria provided clinical testing
Center for Human Genetics, Inc RCV000466535 SCV000781870 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000466535 SCV000542011 uncertain significance Neurofibromatosis, type 1 2018-09-10 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 93 of the NF1 protein (p.Cys93Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with neurofibromatosis type 1 (PMID: 10862084, Invitae). ClinVar contains an entry for this variant (Variation ID: 68328). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Cys93 amino acid residue in NF1. Other variants that disrupt this residue have been observed in affected individuals (PMID: 17426081, 23668869), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.
UniProtKB/Swiss-Prot RCV000059180 SCV000090709 not provided not provided no assertion provided not provided

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