Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189788 | SCV000243436 | uncertain significance | not provided | 2014-01-16 | criteria provided, single submitter | clinical testing | p.Leu430Gln (CTG>CAG): c.1289 T>A in exon 11 of the TPP1 gene (NM_000391.3)The Leu430Gln missense change in the TPP1 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of a non-polar Leucine residue with a polar Glutamine residue. It alters a position that is conserved across species, and other missense mutations associated with neuronal ceroid lipofuscinosis have been reported in this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, based on the currently available information, it is unclear whether Leu430Gln is a disease-causing mutation or a rare benign variant and is interpreted to be of uncertain significance. The variant is found in EPILEPSY panel(s). |
Invitae | RCV000189788 | SCV002113851 | uncertain significance | not provided | 2021-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with glutamine at codon 430 of the TPP1 protein (p.Leu430Gln). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is not present in population databases (ExAC no frequency). 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: 207591). 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. |
Ambry Genetics | RCV002517022 | SCV003643327 | uncertain significance | Inborn genetic diseases | 2022-09-06 | criteria provided, single submitter | clinical testing | The c.1289T>A (p.L430Q) alteration is located in exon 11 (coding exon 11) of the TPP1 gene. This alteration results from a T to A substitution at nucleotide position 1289, causing the leucine (L) at amino acid position 430 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001828010 | SCV002094817 | uncertain significance | Neuronal ceroid lipofuscinosis 2 | 2021-05-14 | no assertion criteria provided | clinical testing |