Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV004555153 | SCV005044066 | likely pathogenic | Surfactant metabolism dysfunction, pulmonary, 2 | 2021-10-22 | criteria provided, single submitter | clinical testing | The c.481C>T p.(Arg161Ter) variant identified in SFTPC has not previously been reported in the literature or public variant repositories (ClinVar and LOVD), and is observed in two alleles across population databases (gnomAD v2.1.1 and v3.1.1, TOPMed Freeze 5 suggesting it is not a common benign variant in the populations represented in those databases. The c.481C>T variant is located in the last translated exon that is part of the BRICHOS domain and predicted to result in a truncated protein devoid of the last ~30 amino acids (>10% of the total protein length) by incorporating a premature termination codon in all encoded transcripts. Both missense variants in the downstream residues and frameshift variants disrupting the last translated exon have been reported in individuals with interstitial lung disease (PMID:11991887, 19443464, 22308375). Functional studies have shown the importance of the residues in the C-terminal BRICHOS domain in proper folding and intracellular trafficking of the proprotein (PMID:23701443). Based on the available evidence this inherited c.481C>T variant is classified here as Likely pathogenic. |