ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.1231_1232del (p.Ser411fs)

dbSNP: rs730881952
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160956 SCV000211664 pathogenic not provided 2020-01-02 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 22331366, 23399955)
Labcorp Genetics (formerly Invitae), Labcorp RCV001054868 SCV001219226 pathogenic Juvenile polyposis syndrome 2022-01-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser411Leufs*17) in the SMAD4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMAD4 are known to be pathogenic (PMID: 16152648, 16436638, 22810475). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia (PMID: 22331366, 23399955). This variant is also known as c.1229_1230delAG. ClinVar contains an entry for this variant (Variation ID: 182867). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003462106 SCV004204864 pathogenic Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 2021-10-13 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003462106 SCV004933712 pathogenic Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 2024-02-09 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
All of Us Research Program, National Institutes of Health RCV003462106 SCV005424219 pathogenic Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 2024-02-28 criteria provided, single submitter clinical testing This variant is predicted to result in loss of protein function through nonsense-mediated decay or protein truncation. Loss of function is an established mechanism of disease. This variant has been reported in multiple individuals with juvenile polyposis syndrome (PMID: 22331366, 23399955, 33097490, 35283344). It is absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/).
Solve-RD Consortium RCV003462106 SCV005200023 likely pathogenic Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 2022-06-01 no assertion criteria provided provider interpretation Variant confirmed as disease-causing by referring clinical team

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