ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.14C>A (p.Ala5Asp) (rs138976576)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723684 SCV000110548 uncertain significance not provided 2016-10-14 criteria provided, single submitter clinical testing
GeneDx RCV000723684 SCV000243445 uncertain significance not provided 2018-12-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TPP1 gene. The A5D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A5D variant is observed in 71/25792 (0.3%) alleles from individuals of Finnish background in large population cohorts (Lek et al., 2016). The A5D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory,University of Chicago RCV000189797 SCV000249174 uncertain significance not specified 2015-04-28 criteria provided, single submitter clinical testing
Invitae RCV001085398 SCV000559672 likely benign Neuronal ceroid lipofuscinosis 2019-12-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000723684 SCV000615825 likely benign not provided 2018-10-25 criteria provided, single submitter clinical testing
Counsyl RCV000674709 SCV000800095 uncertain significance Ceroid lipofuscinosis neuronal 2 2018-05-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000720654 SCV000851533 uncertain significance Seizures 2018-07-17 criteria provided, single submitter clinical testing Insufficient evidence
CeGaT Praxis fuer Humangenetik Tuebingen RCV000723684 SCV001148177 uncertain significance not provided 2018-09-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000674709 SCV001262905 uncertain significance Ceroid lipofuscinosis neuronal 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.