Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001236501 | SCV001409227 | uncertain significance | Aortic valve disease 2 | 2021-10-27 | 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. This sequence change replaces alanine, a(n) neutral and non-polar amino acid, with valine, a(n) neutral and non-polar amino acid, at codon 86 of the SMAD6 protein (p.Ala86Val). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 962614). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. |
Ambry Genetics | RCV004671287 | SCV005167197 | uncertain significance | Inborn genetic diseases | 2024-06-05 | criteria provided, single submitter | clinical testing | The c.257C>T (p.A86V) alteration is located in exon 1 (coding exon 1) of the SMAD6 gene. This alteration results from a C to T substitution at nucleotide position 257, causing the alanine (A) at amino acid position 86 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |