Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001309378 | SCV001498874 | uncertain significance | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 123 of the INF2 protein (p.Gly123Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with INF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1011558). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt INF2 protein function with a negative predictive value of 95%. 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. |
| Ambry Genetics | RCV002543518 | SCV003757445 | uncertain significance | Inborn genetic diseases | 2022-10-26 | criteria provided, single submitter | clinical testing | The c.368G>A (p.G123D) alteration is located in exon 2 (coding exon 1) of the INF2 gene. This alteration results from a G to A substitution at nucleotide position 368, causing the glycine (G) at amino acid position 123 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| ARUP Laboratories, |
RCV003120545 | SCV003800312 | uncertain significance | not provided | 2022-03-09 | criteria provided, single submitter | clinical testing | The INF2 c.368G>A; p.Gly123Asp variant (rs994483790), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1011558). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The glycine at codon 123 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.374). Due to limited information, the clinical significance of this variant is uncertain at this time. |
| Ce |
RCV003120545 | SCV004135277 | uncertain significance | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | INF2: PM2, PP2 |