Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002318248 | SCV000851539 | uncertain significance | Inborn genetic diseases | 2017-02-08 | criteria provided, single submitter | clinical testing | The p.P434S variant (also known as c.1300C>T), located in coding exon 11 of the TPP1 gene, results from a C to T substitution at nucleotide position 1300. The proline at codon 434 is replaced by serine, an amino acid with similar properties. This amino acid position is not well 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 variant remains unclear. |
Ce |
RCV001532627 | SCV001748274 | uncertain significance | not provided | 2021-04-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001532627 | SCV002195020 | uncertain significance | not provided | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 434 of the TPP1 protein (p.Pro434Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TPP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 590066). 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 not expected to disrupt TPP1 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. |
Natera, |
RCV001830594 | SCV002094816 | uncertain significance | Neuronal ceroid lipofuscinosis 2 | 2020-09-17 | no assertion criteria provided | clinical testing |