ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.374C>T (p.Thr125Ile)

gnomAD frequency: 0.00001  dbSNP: rs759468399
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000761913 SCV000892134 likely benign not provided 2018-09-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001340954 SCV001534788 uncertain significance Aortic valve disease 2 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 125 of the SMAD6 protein (p.Thr125Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. ClinVar contains an entry for this variant (Variation ID: 623871). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics RCV003372836 SCV004098396 uncertain significance Inborn genetic diseases 2023-06-18 criteria provided, single submitter clinical testing The p.T125I variant (also known as c.374C>T), located in coding exon 1 of the SMAD6 gene, results from a C to T substitution at nucleotide position 374. The threonine at codon 125 is replaced by isoleucine, an amino acid with 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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