ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.83G>A (p.Arg28Gln)

gnomAD frequency: 0.00002  dbSNP: rs369126677
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000516351 SCV000615831 uncertain significance not specified 2016-09-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002316473 SCV000851361 likely benign Inborn genetic diseases 2017-12-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001298569 SCV001487629 uncertain significance not provided 2020-08-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 28 of the TPP1 protein (p.Arg28Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs369126677, ExAC 0.002%). This variant has not been reported in the literature in individuals with TPP1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV001298569 SCV001788483 uncertain significance not provided 2019-11-11 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001274547 SCV001458798 uncertain significance Neuronal ceroid lipofuscinosis 2 2020-04-14 no assertion criteria provided clinical testing

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