Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001871934 | SCV002308341 | uncertain significance | Hereditary hyperferritinemia with congenital cataracts; Neuroferritinopathy | 2023-06-24 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs543242420, gnomAD 0.008%). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1049905). This variant has not been reported in the literature in individuals affected with FTL-related conditions. This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 52 of the FTL protein (p.Phe52Cys). |
| Ambry Genetics | RCV002548515 | SCV003721427 | likely benign | Inborn genetic diseases | 2022-04-08 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Department of Pathology and Laboratory Medicine, |
RCV001356574 | SCV001551782 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The FTL p.Phe52Cys variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs543242420) and in control databases in 10 of 282810 chromosomes at a frequency of 0.000035 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European (non-Finnish) population in 10 of 129144 chromosomes (freq: 0.000077), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. Although the p.Phe52 residue is not conserved in mammals and other organisms, computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein. The variant occurs outside of the splicing consensus sequence and 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. |