Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001048583 | SCV001212596 | uncertain significance | Fanconi anemia complementation group E | 2022-08-09 | 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 450 of the FANCE protein (p.Thr450Ile). This variant is present in population databases (rs201970876, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with FANCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 845507). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Genetic Services Laboratory, |
RCV001819762 | SCV002069974 | uncertain significance | not specified | 2019-12-13 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the FANCE gene demonstrated a sequence change, c.1349C>T, in exon 8 that results in an amino acid change, p.Thr450Ile. This sequence change does not appear to have been previously described in patients with FANCE-related disorders and has been described in the gnomAD database with a low population frequency of 0.098% in South East Asian subpopulation (rs201970876). The p.Thr450Ile change affects a moderately conserved amino acid residue located in a domain of the FANCE protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Thr450Ile substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Thr450Ile change remains unknown at this time. |
Fulgent Genetics, |
RCV001048583 | SCV002775594 | uncertain significance | Fanconi anemia complementation group E | 2021-09-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002552646 | SCV003702265 | likely benign | Inborn genetic diseases | 2021-10-06 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |