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Background Familial pulmonary fibrosis (FPF) is defined as the presence of at least two affected first-degree relatives and accounts for ~10% of fibrotic ILD. Identifying an underlying monogenic cause is important for optimal patient management e.g. of extra-pulmonary features of telomere biology disorders (TBDs) or cancer surveillance (surfactant biology disorders) and for family screening to identify preclinical disease. The national test directory R421 panel, available from 2022, comprises 27 ILD-associated genes. We wished to review the outcomes of R421 testing from the regional FPF clinic at Royal Papworth to determine whether we can identify those likely to have positive findings through their clinical features, and to better inform patients about testing outcomes.Methods We reviewed records of all patients within the FPF clinic at Royal Papworth who had undergone R421 genetic testing. We recorded genetic test results, demographics, family history, clinical data (FBC/LFT abnormalities, premature greying, history of malignancy) and radiology.Results Seventy-four individuals had the R421 panel sent. Sixty-seven had at least one affected first-degree relative; others had early onset disease (n=5) or clinical suspicion of a TBD (n=2). Seventeen (23%) had a pathogenic variant or likely pathogenic VUS ( figure 1A). All 17 were variants in telomere-related genes (RTEL1 (n=6), PARN (n=5), TERT (n=5) and TERC (n=1), (figure 1B)) with no surfactant biology-related variants found. Those with pathogenic variants were a similar age to those without (64.4 vs 61 yrs, p>0.05) and radiological pattern did not predict genetic result, with UIP being commonest (41% variant found; 36% no variant found). Those with pathogenic variants were more likely to have an FBC abnormality (47% vs 16%, p<0.05); no other clinical features associated with genetic diagnosis.Abstract P96 Figure 1Results of R421 testing. (A) Proportion of results which identified no variant, a pathogenic variant or a likely pathogenic variant of uncertain significance (VUS). (B) Genes in which pathogenic or likely pathogenic variants were locatedConclusions Even within a cohort of individuals with a high pretest probability of a monogenic inherited ILD, <1/4 had a causal variant identified. Demographics and radiology were unable to predict a genetic result but those with an incidentally found FBC abnormality (macrocytosis/anaemia/thrombocytopenia) were more likely to have a TBD. These data highlight the challenges identifying those with monogenic ILDs before genetic testing. Studying larger cohorts may help us better understand predictors of genetic testing outcomes.