ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.1346C>T (p.Ala449Val)

gnomAD frequency: 0.00001  dbSNP: rs1186486223
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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 RCV002001548 SCV002271423 uncertain significance Aortic valve disease 2 2021-08-19 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This sequence change replaces alanine with valine at codon 449 of the SMAD6 protein (p.Ala449Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions.
Ambry Genetics RCV003303583 SCV004007153 uncertain significance Inborn genetic diseases 2024-04-08 criteria provided, single submitter clinical testing The c.1346C>T (p.A449V) alteration is located in exon 4 (coding exon 4) of the SMAD6 gene. This alteration results from a C to T substitution at nucleotide position 1346, causing the alanine (A) at amino acid position 449 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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