Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV002476632 | SCV002786913 | uncertain significance | Glomerulopathy with fibronectin deposits 2; Spondylometaphyseal dysplasia - Sutcliffe type | 2021-07-12 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001356595 | SCV004628331 | likely benign | not provided | 2023-11-03 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001356595 | SCV001551808 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The FN1 p.Glu1097Lys variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs753807100) and in control databases in 8 of 282710 chromosomes at a frequency of 0.0000283 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 4 of 24970 chromosomes (freq: 0.00016), East Asian in 1 of 19952 chromosomes (freq: 0.00005) and European (non-Finnish) in 3 of 129038 chromosomes (freq: 0.000023), but was not observed in the Latino, Ashkenazi Jewish, European (Finnish), Other, and South Asian populations. The p.Glu1097 residue is highly conserved across mammals and other organisms and three out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest an impact to the protein. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |