ClinVar Miner

Submissions for variant NM_014159.6(SETD2):c.1885A>G (p.Lys629Glu) (rs145650484)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000652623 SCV000895585 uncertain significance Luscan-lumish syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000652623 SCV000774494 uncertain significance Luscan-lumish syndrome 2017-11-02 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 629 of the SETD2 protein (p.Lys629Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs145650484, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with SETD2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional 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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