Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001914576 | SCV002143944 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 322 of the ACD protein (p.Ile322Phe). This variant is present in population databases (rs757807430, gnomAD 0.003%). This missense change has been observed in individual(s) with melanoma (PMID: 25505254). ClinVar contains an entry for this variant (Variation ID: 1378295). 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 expected to disrupt ACD protein function with a positive predictive value of 80%. 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. |
Center for Genomic Medicine, |
RCV002268583 | SCV002551718 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing |