Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000804021 | SCV000943911 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 261 of the TPP1 protein (p.Val261Ala). This variant is present in population databases (rs146136938, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of TPP1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 649155). 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 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. |
Gene |
RCV000804021 | SCV001777935 | uncertain significance | not provided | 2019-12-04 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002406787 | SCV002669258 | uncertain significance | Inborn genetic diseases | 2019-06-24 | criteria provided, single submitter | clinical testing | The p.V261A variant (also known as c.782T>C), located in coding exon 7 of the TPP1 gene, results from a T to C substitution at nucleotide position 782. The valine at codon 261 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, alanine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001825589 | SCV002094855 | uncertain significance | Neuronal ceroid lipofuscinosis 2 | 2021-03-28 | no assertion criteria provided | clinical testing |