ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1676_1677CT[1] (p.Leu560fs) (rs759664259)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000819442 SCV000960102 pathogenic Neuronal ceroid lipofuscinosis 2018-09-12 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the TPP1 gene (p.Leu560Thrfs*47). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acids of the TPP1 protein and extend the protein by an additional 42 amino acids. This variant is present in population databases (rs759664259, ExAC 0.003%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with CLN2 disease (Invitae) and has been observed as homozygous or in combination with other TPP1 variants in individuals affected with CLN2 disease (PMID: 10330339, 21990111). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the disrupted amino acids is currently unknown. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001092691 SCV001249318 pathogenic not provided 2017-07-01 criteria provided, single submitter clinical testing

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