ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1543C>T (p.Leu515Phe)

gnomAD frequency: 0.00001  dbSNP: rs748345018
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189794 SCV000243442 uncertain significance not provided 2018-11-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TPP1 gene. The L515F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L515F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000189794 SCV001384407 likely benign not provided 2024-12-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002399705 SCV002705094 uncertain significance Inborn genetic diseases 2024-10-28 criteria provided, single submitter clinical testing The c.1543C>T (p.L515F) alteration is located in exon 12 (coding exon 12) of the TPP1 gene. This alteration results from a C to T substitution at nucleotide position 1543, causing the leucine (L) at amino acid position 515 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001274536 SCV001458783 uncertain significance Neuronal ceroid lipofuscinosis 2 2020-04-14 no assertion criteria provided clinical testing

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