Submissions for variant NM_000391.4(TPP1):c.1542A>T (p.Gly514=)

gnomAD frequency: 0.19057  dbSNP: rs1128396

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000118652	SCV000303961	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000601152	SCV000373318	benign	Neuronal ceroid lipofuscinosis 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587812	SCV000696663	benign	not provided	2016-04-12	criteria provided, single submitter	clinical testing	Variant summary: The TPP1 c.1542A>T variant affects a non-conserved nucleotide, resulting in synonymous amino acid change. 3/5 splice-site tools via Alamut predict that this variant does not affect normal splicing. However, these predictions are not confirmed by experimental studies. This variant was found in 23452/121346 control chromosomes from the large and broad populations of ExAC (including 2381 homozygotes) at a frequency of 0.1932655, which is about 65 times greater than the maximal expected frequency of a pathogenic Tpp1 allele (0.002958). Therefore, the variant is a common benign polymorphism. It has been classified as likely benign by one laboratory before the ExAC control database was commonly used. Taken together, this variant has been classified as Benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000601152	SCV000744906	benign	Neuronal ceroid lipofuscinosis 2	2017-06-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000587812	SCV000844500	benign	not provided	2018-05-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312515	SCV000846002	benign	Inborn genetic diseases	2016-01-08	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000587812	SCV001725247	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000601152	SCV001755076	benign	Neuronal ceroid lipofuscinosis 2	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001538063	SCV001755077	benign	Autosomal recessive spinocerebellar ataxia 7	2021-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000587812	SCV001850611	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000118652	SCV005087816	benign	not specified	2024-07-15	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 32. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV000587812	SCV005322102	benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000118652	SCV000153066	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000601152	SCV000733088	benign	Neuronal ceroid lipofuscinosis 2		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000587812	SCV000801135	benign	not provided	2015-10-23	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000601152	SCV001455822	benign	Neuronal ceroid lipofuscinosis 2	2020-09-16	no assertion criteria provided	clinical testing