Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Johns Hopkins Genomics, |
RCV000758242 | SCV000886882 | uncertain significance | Surfactant metabolism dysfunction, pulmonary, 1 | 2019-02-08 | criteria provided, single submitter | clinical testing | SFTPB c.352G>A has not been reported in ClinVar nor the literature, to our knowledge. This variant (rs45557339) is rare in large population datasets (gnomAD: 68/282654 alleles; 0.02406%, no homozygotes). Two bioinformatic tools queried predict that this substitution would be tolerated, and the aspartic acid residue at this position is not evolutionarily conserved across species assessed. Due to insufficient evidence that this variant is deleterious, the clinical significance of c.352G>A is uncertain at this time. |
| Ambry Genetics | RCV002352266 | SCV002623554 | uncertain significance | Hereditary pulmonary alveolar proteinosis | 2023-09-29 | criteria provided, single submitter | clinical testing | The c.388G>A (p.D130N) alteration is located in exon 5 (coding exon 4) of the SFTPB gene. This alteration results from a G to A substitution at nucleotide position 388, causing the aspartic acid (D) at amino acid position 130 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003574808 | SCV004332098 | uncertain significance | not provided | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 130 of the SFTPB protein (p.Asp130Asn). This variant is present in population databases (rs45557339, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with SFTPB-related conditions. ClinVar contains an entry for this variant (Variation ID: 619287). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SFTPB protein function with a negative predictive value of 80%. 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. |
| Department of Pathology and Laboratory Medicine, |
RCV000758242 | SCV006055610 | uncertain significance | Surfactant metabolism dysfunction, pulmonary, 1 | 2023-10-04 | criteria provided, single submitter | research |