ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.305C>G (p.Thr102Arg) (rs754706111)

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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 RCV000622909 SCV000741143 likely pathogenic Inborn genetic diseases 2016-01-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Invitae RCV000689010 SCV000816645 uncertain significance Legius syndrome 2018-03-14 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 102 of the SPRED1 protein (p.Thr102Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a mother and her son affected with Legius syndrome (PMID: 19920235). Experimental studies have shown that this missense change affects the inhibition of ERK activation and severely reduces binding affinity to the GTPase-activating protein (GAP)-related domain (GRD) of neurofibromin (PMID: 19920235, 22751498, 21089071). 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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