Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001070098 | SCV001235310 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2022-06-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 342 of the ACD protein (p.Pro342Leu). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 863188). This variant has not been reported in the literature in individuals affected with ACD-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. |
| Ambry Genetics | RCV002379622 | SCV002692447 | uncertain significance | Inborn genetic diseases | 2021-08-13 | criteria provided, single submitter | clinical testing | The p.P342L variant (also known as c.1025C>T), located in coding exon 9 of the ACD gene, results from a C to T substitution at nucleotide position 1025. The proline at codon 342 is replaced by leucine, 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. |