Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002441007 | SCV002746034 | uncertain significance | Inborn genetic diseases | 2025-11-03 | criteria provided, single submitter | clinical testing | The c.1120G>A (p.E374K) alteration is located in exon 10 (coding exon 10) of the ACD gene. This alteration results from a G to A substitution at nucleotide position 1120, causing the glutamic acid (E) at amino acid position 374 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001901600 | SCV002173217 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2026-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 374 of the ACD protein (p.Glu374Lys). This variant is present in population databases (rs200298308, gnomAD 0.03%). 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: 1404342). 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 not expected to disrupt ACD protein function with a negative 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. |
| Prevention |
RCV003911089 | SCV004727690 | uncertain significance | ACD-related disorder | 2023-10-28 | no assertion criteria provided | clinical testing | The ACD c.1120G>A variant is predicted to result in the amino acid substitution p.Glu374Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-67692233-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |