ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.620del (p.Asn207fs)

dbSNP: rs2144419362
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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 RCV001386065 SCV001586155 pathogenic Juvenile polyposis syndrome 2022-11-01 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with SMAD4-related conditions. This sequence change creates a premature translational stop signal (p.Asn207Metfs*34) 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). ClinVar contains an entry for this variant (Variation ID: 1073157). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV004995731 SCV005503057 pathogenic Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome 2024-10-03 criteria provided, single submitter clinical testing The c.620delA pathogenic mutation, located in coding exon 4 of the SMAD4 gene, results from a deletion of one nucleotide at nucleotide position 620, causing a translational frameshift with a predicted alternate stop codon (p.N207Mfs*34). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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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