ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.512C>T (p.Ser171Leu)

dbSNP: rs1568205010
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687533 SCV000815105 uncertain significance Juvenile polyposis syndrome 2022-05-02 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 171 of the SMAD4 protein (p.Ser171Leu). 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: 567445). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SMAD4 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sema4, Sema4 RCV002257927 SCV002538328 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-28 criteria provided, single submitter curation
Ambry Genetics RCV002334262 SCV002644716 uncertain significance Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome 2020-03-23 criteria provided, single submitter clinical testing The p.S171L variant (also known as c.512C>T), located in coding exon 4 of the SMAD4 gene, results from a C to T substitution at nucleotide position 512. The serine at codon 171 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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