Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002411583 | SCV002676252 | uncertain significance | Inborn genetic diseases | 2024-08-20 | criteria provided, single submitter | clinical testing | The c.857C>T (p.T286I) alteration is located in exon 7 (coding exon 7) of the ACD gene. This alteration results from a C to T substitution at nucleotide position 857, causing the threonine (T) at amino acid position 286 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Johns Hopkins Genomics, |
RCV001064127 | SCV001469037 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2020-12-08 | criteria provided, single submitter | clinical testing | This ACD variant (rs1181866888) is rare (<0.1%) in a large population dataset (gnomAD: 4/251072 total alleles; 0.002%; no homozygotes) and has not been reported in the literature, to our knowledge. This variant has been reported in ClinVar. Two bioinformatic tools queried predict that this substitution would be damaging, and the threonine residue at this position is evolutionarily conserved across most mammals assessed. We consider the clinical significance of c.848C>T to be uncertain at this time. |
| Labcorp Genetics |
RCV001064127 | SCV001229006 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2025-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 286 of the ACD protein (p.Thr286Ile). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ACD-related conditions. ClinVar contains an entry for this variant (Variation ID: 858283). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |