ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.381-10dup

gnomAD frequency: 0.02726  dbSNP: rs146315473
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178763 SCV000230917 benign not specified 2014-09-03 criteria provided, single submitter clinical testing
GeneDx RCV000675465 SCV000245330 benign not provided 2018-06-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000178763 SCV000303963 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000340409 SCV000373334 likely benign Neuronal Ceroid-Lipofuscinosis, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000675465 SCV000559667 benign not provided 2024-02-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000675465 SCV001146222 benign not provided 2018-11-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000178763 SCV002600697 benign not specified 2022-10-24 criteria provided, single submitter clinical testing Variant summary: TPP1 c.381-10dupT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0089 in 282666 control chromosomes, predominantly at a frequency of 0.089 within the African or African-American subpopulation in the gnomAD database, including 102 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 45 fold of the estimated maximal expected allele frequency for a pathogenic variant in TPP1 causing Neuronal Ceroid-Lipofuscinosis (Batten Disease) phenotype (0.002), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.381-10dupT in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) and no experimental evidence demonstrating its impact on protein function have been reported. Seven ClinVar submitters (evaluation after 2014) cite the variant as benign (n=5), likely benign (n=1) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000675465 SCV000801152 benign not provided 2017-08-30 no assertion criteria provided clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000678677 SCV000803211 likely pathogenic Neuronal ceroid lipofuscinosis 2 2018-02-05 no assertion criteria provided clinical testing The observed variant g.7024dupT was neither found in 1000 Genomes nor in ExAC databases. The in-silico prediction of the given variant is disease causing by MutationTaster2.
Natera, Inc. RCV000678677 SCV001459954 benign Neuronal ceroid lipofuscinosis 2 2020-09-16 no assertion criteria provided clinical testing

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