ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.1106A>G (p.Asn369Ser) (rs139569694)

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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 RCV000131130 SCV000186062 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000131130 SCV000686514 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-29 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764163 SCV000895165 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 RCV000555043 SCV000632748 uncertain significance Juvenile polyposis syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 369 of the SMAD4 protein (p.Asn369Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs139569694, ExAC 0.01%). This variant has been reported in an individual with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 142165). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
PreventionGenetics RCV000679584 SCV000806689 uncertain significance not provided 2017-06-28 criteria provided, single submitter clinical testing

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