Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001999366 | SCV002278213 | uncertain significance | not provided | 2024-09-29 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 906 of the FN1 protein (p.Thr906Ile). This variant is present in population databases (rs370342980, gnomAD 0.01%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with FN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1498737). 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) indicates that this missense variant is not expected to disrupt FN1 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. |
| Fulgent Genetics, |
RCV002486614 | SCV002789336 | likely benign | Glomerulopathy with fibronectin deposits 2; Spondylometaphyseal dysplasia - Sutcliffe type | 2024-04-05 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002642068 | SCV003680861 | uncertain significance | Inborn genetic diseases | 2022-05-27 | criteria provided, single submitter | clinical testing | The c.2717C>T (p.T906I) alteration is located in exon 19 (coding exon 19) of the FN1 gene. This alteration results from a C to T substitution at nucleotide position 2717, causing the threonine (T) at amino acid position 906 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV004746573 | SCV005364715 | uncertain significance | FN1-related disorder | 2024-04-12 | no assertion criteria provided | clinical testing | The FN1 c.2717C>T variant is predicted to result in the amino acid substitution p.Thr906Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |