ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.585C>G (p.Tyr195Ter)

dbSNP: rs1316902116
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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 RCV002233154 SCV000815032 pathogenic Juvenile polyposis syndrome 2018-04-09 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with SMAD4-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr195*) in the SMAD4 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SMAD4 are known to be pathogenic (PMID: 16152648, 16436638, 22810475).
Ambry Genetics RCV002352125 SCV002647665 pathogenic Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome 2018-10-21 criteria provided, single submitter clinical testing The p.Y195* pathogenic mutation (also known as c.585C>G), located in coding exon 4 of the SMAD4 gene, results from a C to G substitution at nucleotide position 585. This changes the amino acid from a tyrosine 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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