Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001066517 | SCV001231530 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2023-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 441 of the ACD protein (p.Pro441Ser). This variant is present in population databases (rs757414908, gnomAD 0.02%). 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: 860243). 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 ACD 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. |
Ambry Genetics | RCV002379598 | SCV002690433 | uncertain significance | Inborn genetic diseases | 2021-07-07 | criteria provided, single submitter | clinical testing | The p.P441S variant (also known as c.1321C>T), located in coding exon 10 of the ACD gene, results from a C to T substitution at nucleotide position 1321. The proline at codon 441 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |
Prevention |
RCV003413886 | SCV004118480 | uncertain significance | ACD-related disorder | 2023-06-09 | criteria provided, single submitter | clinical testing | The ACD c.1321C>T variant is predicted to result in the amino acid substitution p.Pro441Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-67692032-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |