Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000575065 | SCV000883266 | likely pathogenic | Spondylometaphyseal dysplasia - Sutcliffe type | 2018-10-15 | criteria provided, single submitter | curation | This variant is interpreted as Likely Pathogenic, for Spondylometaphyseal dysplasia, corner fracture type, autosomal dominant. The following ACMG Tag(s) were applied: PM6 => Assumed de novo, but without confirmation of paternity and maternity (https://www.ncbi.nlm.nih.gov/pubmed/29100092). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 => Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation. Replaces a cysteine involved in disulfid (http://www.uniprot.org/uniprot/P02751). |
| Invitae | RCV002526994 | SCV003524898 | pathogenic | not provided | 2022-07-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 424644). This missense change has been observed in individual(s) with spondylometaphyseal dysplasia, 'corner fracture' type (PMID: 29100092). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 123 of the FN1 protein (p.Cys123Arg). |
| CHU Sainte- |
RCV000509582 | SCV000574554 | likely pathogenic | Spondylometaphyseal dysplasia | 2017-02-25 | no assertion criteria provided | research | 6 Individuals with novel FN1 mutations and spondylometaphyseal dysplasia |
| OMIM | RCV000575065 | SCV000676923 | pathogenic | Spondylometaphyseal dysplasia - Sutcliffe type | 2017-12-28 | no assertion criteria provided | literature only |