ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.547C>T (p.Gln183Ter)

dbSNP: rs1555685645
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001040938 SCV001204530 pathogenic Juvenile polyposis syndrome 2023-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln183*) 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 variant has not been reported in the literature in individuals affected with SMAD4-related conditions. ClinVar contains an entry for this variant (Variation ID: 839230). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002348352 SCV002651220 pathogenic Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome 2018-12-20 criteria provided, single submitter clinical testing The p.Q183* pathogenic mutation (also known as c.547C>T), located in coding exon 4 of the SMAD4 gene, results from a C to T substitution at nucleotide position 547. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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