ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.463A>G (p.Ser155Gly) (rs1057519259)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000415677 SCV000493804 uncertain significance Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 2016-01-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563891 SCV000676268 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000707389 SCV000836485 uncertain significance Juvenile polyposis syndrome 2018-12-25 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 155 of the SMAD4 protein (p.Ser155Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with vascular anomalies (PMID: 28655553). ClinVar contains an entry for this variant (Variation ID: 374977). 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: "Deleterious"; PolyPhen-2: "Benign"; 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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