ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.1219G>C (p.Val407Leu) (rs147621330)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562603 SCV000671973 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000562603 SCV000910026 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-17 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764164 SCV000895166 uncertain significance Myhre syndrome; Juvenile polyposis syndrome; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Carcinoma of pancreas 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000558005 SCV000632754 uncertain significance Juvenile polyposis syndrome 2018-12-15 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 407 of the SMAD4 protein (p.Val407Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs147621330, ExAC 0.003%). This variant has not been reported in the literature in individuals with SMAD4-related disease. ClinVar contains an entry for this variant (Variation ID: 460530). 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: "Probably Damaging"; Align-GVGD: "Class C25"). 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.
True Health Diagnostics RCV000562603 SCV000788212 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-22 no assertion criteria provided clinical testing

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