Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000188166 | SCV000241773 | uncertain significance | not provided | 2022-05-20 | criteria provided, single submitter | clinical testing | Identified in a cohort of individuals with epilepsy and neurodevelopmental disorders; however, detailed clinical and segregation data was not provided (Lindy et al., 2018); Published functional studies demonstrate the Y121C variant does not have an effect on protein localization (Sharifi et al, 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20826447, 29655203, 18850119) |
| Invitae | RCV000001059 | SCV000639423 | uncertain significance | Neuronal ceroid lipofuscinosis 7 | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 121 of the MFSD8 protein (p.Tyr121Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with late infantile neuronal ceroid lipofuscinoses in 3 siblings (PMID: 18850119). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1004). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change does not substantially affect MFSD8 function (PMID: 20826447). 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. |
| OMIM | RCV000001059 | SCV000021209 | pathogenic | Neuronal ceroid lipofuscinosis 7 | 2009-02-01 | no assertion criteria provided | literature only |