Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Genomic Medicine, |
RCV000191960 | SCV003924334 | uncertain significance | Brown-Vialetto-van Laere syndrome 1 | 2023-05-08 | criteria provided, single submitter | research | |
| Invitae | RCV000191960 | SCV004298452 | likely pathogenic | Brown-Vialetto-van Laere syndrome 1 | 2023-03-14 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects SLC52A3 function (PMID: 22273710). 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 expected to disrupt SLC52A3 protein function. ClinVar contains an entry for this variant (Variation ID: 210015). This missense change has been observed in individual(s) with Brown-Vialetto-Van Laere syndrome (PMID: 20920669). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs267606683, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 71 of the SLC52A3 protein (p.Glu71Lys). |
| Gene |
RCV000191960 | SCV000246212 | not provided | Brown-Vialetto-van Laere syndrome 1 | no assertion provided | literature only |