ClinVar Miner

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

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Total submissions: 12
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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 likely benign not provided 2021-06-25 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge
Genetic Services Laboratory, University of Chicago RCV000189797 SCV000249174 uncertain significance not specified 2015-04-28 criteria provided, single submitter clinical testing
Invitae RCV000723684 SCV000559672 likely benign not provided 2020-12-08 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 The p.A5D variant (also known as c.14C>A), located in coding exon 1 of the TPP1 gene, results from a C to A substitution at nucleotide position 14. The alanine at codon 5 is replaced by aspartic acid, an amino acid with dissimilar 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000723684 SCV001148177 likely benign not provided 2021-06-01 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001280958 SCV001468330 uncertain significance Ceroid lipofuscinosis neuronal 2; Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia 2020-05-13 criteria provided, single submitter clinical testing TPP1 NM_000391.3 exon 1 p.Ala5Asp (c.14C>A): This variant has not been reported in the literature but is present in 0.2% (70/25122) of Finnish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/11-6640618-G-T?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:92884). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Baylor Genetics RCV000674709 SCV001528401 uncertain significance Ceroid lipofuscinosis neuronal 2 2018-02-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Natera, Inc. RCV000674709 SCV001458799 uncertain significance Ceroid lipofuscinosis neuronal 2 2020-04-14 no assertion criteria provided clinical testing

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