Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetics Service, |
RCV000850247 | SCV000902255 | likely pathogenic | Osteogenesis imperfecta type 5 | 2018-01-03 | criteria provided, single submitter | clinical testing | The Ser40Trp variant in IFITM5 was absent from population studies. Ser40Leu variant results in severe OI phenotype. This Ser40Trp co-segregate with affected individuals in the family. In summary, the Ser40Trp variant meets our criteria to be classified as likely pathogenic variant. |
Invitae | RCV002536171 | SCV002949889 | pathogenic | not provided | 2023-08-09 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 40 of the IFITM5 protein (p.Ser40Trp). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 30985308, 34567078). ClinVar contains an entry for this variant (Variation ID: 689498). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Ser40 amino acid residue in IFITM5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24478195, 24519609, 29595812). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000850247 | SCV002097241 | pathogenic | Osteogenesis imperfecta type 5 | 2022-02-11 | no assertion criteria provided | literature only |