ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1307T>C (p.Leu436Pro)

gnomAD frequency: 0.00031  dbSNP: rs150039898
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678854 SCV000805045 uncertain significance Seizure 2017-04-04 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000993341 SCV001146221 uncertain significance not provided 2018-11-26 criteria provided, single submitter clinical testing
GeneDx RCV000993341 SCV001803072 uncertain significance not provided 2021-03-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000993341 SCV002249966 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 436 of the TPP1 protein (p.Leu436Pro). This variant is present in population databases (rs150039898, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with TPP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 457937). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TPP1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Laboratories, Mayo Clinic RCV000993341 SCV002541124 uncertain significance not provided 2021-06-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002525290 SCV003720319 uncertain significance Inborn genetic diseases 2021-07-14 criteria provided, single submitter clinical testing The c.1307T>C (p.L436P) alteration is located in exon 11 (coding exon 11) of the TPP1 gene. This alteration results from a T to C substitution at nucleotide position 1307, causing the leucine (L) at amino acid position 436 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001273172 SCV001455827 uncertain significance Neuronal ceroid lipofuscinosis 2 2020-09-16 no assertion criteria provided clinical testing

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