Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002030845 | SCV002309961 | pathogenic | not provided | 2024-11-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 208 of the ABCA3 protein (p.Arg208Trp). This variant is present in population databases (rs768483175, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of autosomal recessive childhood interstitial lung disease (PMID: 17517255, 18024538, 22068586, 24871971). ClinVar contains an entry for this variant (Variation ID: 1520597). Invitae Evidence 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 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 ABCA3 protein function. For these reasons, this variant has been classified as Pathogenic. |
| Neuberg Centre For Genomic Medicine, |
RCV003339905 | SCV004047337 | likely pathogenic | Interstitial lung disease due to ABCA3 deficiency | 2023-05-20 | criteria provided, single submitter | clinical testing | The missense c.622C>T (p.Arg208Trp) variant in the ABCA3 gene has been observed in individuals with clinical features of autosomal recessive childhood interstitial lung disease (Kröner, Carolin et al.,2017). This variant is reported with the allele frequency (0.002%) in the gnomAD Exomes. The amino acid Arginine at position 208 is changed to a Trptophan changing protein sequence and it might alter its composition and physico-chemical properties. It is submitted to ClinVar as Likely Pathogenic. Multiple lines of computational evidence (Polyphen - Damaging, SIFT – Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The amino acid change p.Arg208Trp in ABCA3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Functional studies are required to prove the pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic. |
| Fulgent Genetics, |
RCV003339905 | SCV005646514 | pathogenic | Interstitial lung disease due to ABCA3 deficiency | 2024-05-15 | criteria provided, single submitter | clinical testing |