Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688974 | SCV000816606 | uncertain significance | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 245 of the TPP1 protein (p.Arg245His). This variant is present in population databases (rs754161261, gnomAD 0.006%). 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: 568573). 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. |
Illumina Laboratory Services, |
RCV001104753 | SCV001261639 | uncertain significance | Neuronal ceroid lipofuscinosis 2 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Gene |
RCV000688974 | SCV001995723 | uncertain significance | not provided | 2019-09-12 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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 | RCV002547134 | SCV003529446 | uncertain significance | Inborn genetic diseases | 2021-08-16 | criteria provided, single submitter | clinical testing | The c.734G>A (p.R245H) alteration is located in exon 7 (coding exon 7) of the TPP1 gene. This alteration results from a G to A substitution at nucleotide position 734, causing the arginine (R) at amino acid position 245 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001104753 | SCV002094857 | uncertain significance | Neuronal ceroid lipofuscinosis 2 | 2021-05-26 | no assertion criteria provided | clinical testing |