ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1300C>T (p.Pro434Ser)

dbSNP: rs1420637772
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002318248 SCV000851539 uncertain significance Inborn genetic diseases 2017-02-08 criteria provided, single submitter clinical testing The p.P434S variant (also known as c.1300C>T), located in coding exon 11 of the TPP1 gene, results from a C to T substitution at nucleotide position 1300. The proline at codon 434 is replaced by serine, 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 variant remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV001532627 SCV001748274 uncertain significance not provided 2021-04-01 criteria provided, single submitter clinical testing
Invitae RCV001532627 SCV002195020 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 434 of the TPP1 protein (p.Pro434Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 590066). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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.
Natera, Inc. RCV001830594 SCV002094816 uncertain significance Neuronal ceroid lipofuscinosis 2 2020-09-17 no assertion criteria provided clinical testing

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