ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1490G>A (p.Arg497His)

gnomAD frequency: 0.00005  dbSNP: rs549928656
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000713860 SCV000628905 uncertain significance not provided 2022-09-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 497 of the TPP1 protein (p.Arg497His). This variant is present in population databases (rs549928656, gnomAD 0.03%). 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: 457942). 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.
Athena Diagnostics Inc RCV000713860 SCV000844498 uncertain significance not provided 2018-04-09 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000713860 SCV001748273 uncertain significance not provided 2021-03-01 criteria provided, single submitter clinical testing
GeneDx RCV000713860 SCV001804668 uncertain significance not provided 2019-03-12 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002497073 SCV002814686 uncertain significance Neuronal ceroid lipofuscinosis 2; Autosomal recessive spinocerebellar ataxia 7 2022-03-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV001273171 SCV001455825 uncertain significance Neuronal ceroid lipofuscinosis 2 2020-09-16 no assertion criteria provided clinical testing

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