Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001205417 | SCV001376672 | uncertain significance | Dyskeratosis congenita, autosomal recessive 6; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 | 2023-10-27 | 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 222 of the PARN protein (p.Pro222Leu). 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. This variant has not been reported in the literature in individuals affected with PARN-related conditions. ClinVar contains an entry for this variant (Variation ID: 936588). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PARN 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. |
| Garcia Pulmonary Genetics Research Laboratory, |
RCV002509628 | SCV002547351 | likely risk allele | Pulmonary fibrosis | 2022-06-09 | no assertion criteria provided | research | Leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted |