ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.221G>T (p.Cys74Phe) (rs1412213561)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547389 SCV000645820 uncertain significance Legius syndrome 2017-05-23 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 74 of the SPRED1 protein (p.Cys74Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with multiple cafe au lait macules with freckling. This individual's mother also carried this variant but was unaffected with any pigmentary lesions or other signs of neurofibromatosis type 1 (PMID: 19920235). Experimental studies have shown that this missense change behaved similarly to wildtype in assays measuring cellular differentiation, neurite outgrowth, Elk-1 and ERK suppression, and binding to the GAP-related domain (GRD) of neurofibromin (PMID: 19920235, 26635368). In summary, this variant is a rare missense change that does not affect protein function in vitro. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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