ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.1134_1135delAG (p.Arg378Serfs) (rs1555686503)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657385 SCV000779118 pathogenic not provided 2017-09-12 criteria provided, single submitter clinical testing This deletion of two nucleotides in SMAD4 is denoted c.1134_1135delAG at the cDNA level and p.Arg378SerfsX14 (R378SfsX14) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AGAG[delAG]CAAG. The deletion causes a frameshift which changes an Arginine to a Serine at codon 378, and creates a premature stop codon at position 14 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000698896 SCV000827586 pathogenic Juvenile polyposis syndrome 2018-02-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg378Serfs*14) in the SMAD4 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SMAD4-related disease. Loss-of-function variants in SMAD4 are known to be pathogenic (PMID: 16152648, 16436638, 22810475). For these reasons, this variant has been classified as Pathogenic.

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