Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001022843 | SCV001184624 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-21 | criteria provided, single submitter | clinical testing | The p.A155V variant (also known as c.464C>T), located in coding exon 4 of the DICER1 gene, results from a C to T substitution at nucleotide position 464. The alanine at codon 155 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved through mammals but not in all available vertebrate species. 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. |
Labcorp Genetics |
RCV003750849 | SCV004396748 | uncertain significance | DICER1-related tumor predisposition | 2023-02-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 155 of the DICER1 protein (p.Ala155Val). ClinVar contains an entry for this variant (Variation ID: 825071). 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) performed at Invitae indicates that this missense variant is not expected to disrupt DICER1 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. |