ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1252C>T (p.Arg418Trp)

gnomAD frequency: 0.00021  dbSNP: rs143584882
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315999 SCV000847793 uncertain significance Inborn genetic diseases 2019-05-24 criteria provided, single submitter clinical testing The p.R418W variant (also known as c.1252C>T), located in coding exon 10 of the TPP1 gene, results from a C to T substitution at nucleotide position 1252. The arginine at codon 418 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Eurofins Ntd Llc (ga) RCV000731066 SCV000858837 uncertain significance not provided 2018-01-16 criteria provided, single submitter clinical testing
Invitae RCV000731066 SCV001498969 uncertain significance not provided 2021-11-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 418 of the TPP1 protein (p.Arg418Trp). This variant is present in population databases (rs143584882, 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: 576289). 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 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.
GeneDx RCV000731066 SCV001786411 uncertain significance not provided 2023-07-28 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
Natera, Inc. RCV001274538 SCV001458785 uncertain significance Neuronal ceroid lipofuscinosis 2 2020-04-14 no assertion criteria provided clinical testing

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