ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.209A>G (p.Lys70Arg)

dbSNP: rs1555685038
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital RCV000505822 SCV000600010 uncertain significance Myhre syndrome 2017-06-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001857243 SCV002311087 uncertain significance Juvenile polyposis syndrome 2023-06-13 criteria provided, single submitter clinical testing 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SMAD4 protein function. ClinVar contains an entry for this variant (Variation ID: 438836). This variant has not been reported in the literature in individuals affected with SMAD4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 70 of the SMAD4 protein (p.Lys70Arg).
Ambry Genetics RCV003159637 SCV003863706 uncertain significance Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome 2023-01-22 criteria provided, single submitter clinical testing The p.K70R variant (also known as c.209A>G), located in coding exon 1 of the SMAD4 gene, results from an A to G substitution at nucleotide position 209. The lysine at codon 70 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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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