Submissions for variant NM_000391.4(TPP1):c.293C>T (p.Thr98Met)

gnomAD frequency: 0.00209  dbSNP: rs140726254

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118653	SCV000153067	uncertain significance	not provided	2014-02-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000186669	SCV000169039	benign	not specified	2013-07-03	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000118653	SCV000284806	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000509378	SCV000373335	uncertain significance	Neuronal ceroid lipofuscinosis 2	2018-01-12	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.
Ambry Genetics	RCV002313926	SCV000848613	uncertain significance	Inborn genetic diseases	2018-02-12	criteria provided, single submitter	clinical testing	The p.T98M variant (also known as c.293C>T), located in coding exon 4 of the TPP1 gene, results from a C to T substitution at nucleotide position 293. The threonine at codon 98 is replaced by methionine, an amino acid with similar 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 alteration remains unclear.
Eurofins Ntd Llc (ga)	RCV000186669	SCV000859381	likely benign	not specified	2018-02-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000509378	SCV001737172	uncertain significance	Neuronal ceroid lipofuscinosis 2	2021-05-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000118653	SCV004135866	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TPP1: BP4, BS2
GenomeConnect, ClinGen	RCV000509378	SCV000607046	not provided	Neuronal ceroid lipofuscinosis 2		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000118653	SCV001978433	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118653	SCV001980549	likely benign	not provided		no assertion criteria provided	clinical testing