Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000698364 | SCV000827024 | uncertain significance | Dyskeratosis congenita, autosomal recessive 6; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 | 2022-01-01 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Tyr91 amino acid residue in PARN. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31448843; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 575994). This variant has not been reported in the literature in individuals affected with PARN-related conditions. This variant is present in population databases (rs764315291, gnomAD 0.005%). This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 91 of the PARN protein (p.Tyr91Asn). |