ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.277A>T (p.Met93Leu)

gnomAD frequency: 0.00010  dbSNP: rs781686740
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000820541 SCV000961258 uncertain significance Aortic valve disease 2 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 93 of the SMAD6 protein (p.Met93Leu). This variant is present in population databases (rs781686740, gnomAD 0.3%). 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: 662804). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Ambry Genetics RCV002434012 SCV002747252 uncertain significance Inborn genetic diseases 2021-11-14 criteria provided, single submitter clinical testing The p.M93L variant (also known as c.277A>T), located in coding exon 1 of the SMAD6 gene, results from an A to T substitution at nucleotide position 277. The methionine at codon 93 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323735 SCV004028942 uncertain significance not specified 2024-03-11 criteria provided, single submitter clinical testing

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