Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000188189 | SCV000241796 | uncertain significance | not provided | 2015-12-03 | criteria provided, single submitter | clinical testing | p.Trp97Cys (W97C) TGG>TGC: c.291 G>C in exon 5 of the MFSD8 gene (NM_152778.2). The W97C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The W97C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is highly across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, other missense mutations in nearby residues have not been reported. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant The variant is found in MFSD8 panel(s). |
| Labcorp Genetics |
RCV000234587 | SCV000291532 | uncertain significance | Neuronal ceroid lipofuscinosis 7 | 2022-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 97 of the MFSD8 protein (p.Trp97Cys). This variant is present in population databases (rs796052749, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with MFSD8-related conditions. ClinVar contains an entry for this variant (Variation ID: 206169). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Duke University Health System Sequencing Clinic, |
RCV000234587 | SCV003919032 | uncertain significance | Neuronal ceroid lipofuscinosis 7 | 2023-04-20 | criteria provided, single submitter | research |