Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690964 | SCV000818695 | uncertain significance | Brown-Vialetto-van Laere syndrome 1 | 2021-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 297 of the SLC52A3 protein (p.Pro297Leu). This variant is present in population databases (rs201990981, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC52A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 570161). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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. |
Ambry Genetics | RCV002369857 | SCV002685389 | uncertain significance | Inborn genetic diseases | 2019-11-11 | criteria provided, single submitter | clinical testing | The p.P297L variant (also known as c.890C>T), located in coding exon 2 of the SLC52A3 gene, results from a C to T substitution at nucleotide position 890. The proline at codon 297 is replaced by leucine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome |
RCV003483708 | SCV004228621 | not provided | Brown-Vialetto-van Laere syndrome 1; Progressive bulbar palsy of childhood | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 02-03-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |