ClinVar Miner

Submissions for variant NM_212482.4(FN1):c.367T>C (p.Cys123Arg)

dbSNP: rs1553667072
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Total submissions: 4
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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 ( 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 (
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-Justine Research Center, University of Montreal 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

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