ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.875C>T (p.Pro292Leu) (rs786201404)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163557 SCV000214115 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761013 SCV000890928 uncertain significance Wilms Tumor 2016-03-02 no assertion criteria provided clinical testing
Color RCV000163557 SCV000686560 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-02 criteria provided, single submitter clinical testing
Invitae RCV000469746 SCV000543758 uncertain significance Juvenile polyposis syndrome 2018-07-03 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 292 of the SMAD4 protein (p.Pro292Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SMAD4-related disease. ClinVar contains an entry for this variant (Variation ID: 184326). 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 C65"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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