Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649963 | SCV000771800 | uncertain significance | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease, dominant intermediate E | 2019-05-24 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 997 of the INF2 protein (p.Asp997Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs370719592, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with INF2-related disease. 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. |
| ARUP Laboratories, |
RCV001285291 | SCV001471698 | uncertain significance | none provided | 2020-02-10 | criteria provided, single submitter | clinical testing | The INF2 c.2989G>A; p.Asp997Asn variant (rs370719592), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 540041). This variant is found in the general population with an overall allele frequency of 0.01% (16/277120 alleles) in the Genome Aggregation Database. The aspartate at codon 997 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Asp997Asn variant is uncertain at this time. |